bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal Development of T Cells
Authors: Pyke K. W. , Papiernik M. , Bach J.-F.
Published: December 2022

The in vitro migration pattern of neonatal spleen cells was studied in a system of grafts: the newborn spleen was grafted under the renal capsule of adult mice, either normal, thymectomized as adults, or T-deprived animals. The influence of thymic humoral factors on these cells was studied by grafting some of the hosts with thymic tissue in cell-impermeable diffusion chambers. The results showed that the cells of the neonatal spleen contain subpopulations that migrate specifically to either the thymus, the spleen, or the lymph nodes and that these migration patterns are not influenced by thymic humoral function. In T-deprived animals; however, in the absence of any thymic influences, cells that migrated to the thymus, only, were present. Under the influence of thymic humoral factors, this thymus-seeking population became minimal while a new population of spleen- and nodeseeking cells was detectable. The results provide evidence to suggest that there is a sequence of maturation in terms of lymphoid organ homing of precursor cells and that one population may generate the succeeding populations. There is also evidence to suggest that a thymic humoral factor may play a role in these changes in migration patterns without necessarily direct correlation with changes in classic criteria of T cell maturation.
In Vitro Adherence of Lymphocytes to Unfixed and Fixed High Endothelial Cells of Lymph Nodes
Authors: Woodruff Judith J. , Rasmussen Robert A.
Published: December 2022

Rat thoracic duct lymphocytes (TDL) bind selectively to venules lined by high endothelial cells (HEV) when overlaid onto glutaraldehyde-fixed frozen sections of lymph nodes. This report describes the characteristics of TDL binding to HEV in unfixed frozen sections and compares this reactivity with that observed after fixing sections with different reagents. We found that TDL bound to unfixed HEV and that the pattern of adherence to such sections was identical to that observed when using glutaraldehyde-fixed tissue. Fixation of the sections with glutaraldehyde, however, enhanced the binding reaction. This effect was also observed when sections were treated with the diimidoester, dimethylsuberimidate (DMS) but not when methanol or formaldehyde was used. Since glutaraldehyde and DMS are each bifunctional cross-linking reagents, the results suggest that in vitro HEV adherence was facilitated under conditions in which the endothelial binding sites were present in an aggregated form.
Role of Self Carriers in the Immune Response and Tolerance
Authors: Jandinski John J. , Scott David W.
Published: December 2022

Previous studies indicated that T cells are required for tolerance induction by hapten-modified syngeneic spleen cells (TNP-SC) in vivo. The role of T cells in the maintenance of this unresponsive state has been examined herein. By three criteria—limiting dilution precursor analysis, removal of T cells by anti-Thy-1 + C, and direct mixing experiments—we show that T cells are required for the continued suppression of the B cell response to the T-independent antigen, TNP-POL. Suppressor cells can also be induced by TNP-teratoma cells, which lack detectable H-2 antigens. Both anti-Ly-1 + C and anti-Ly-2 + C treatment reversed suppression induced by TNP-SC. These results demonstrate that normal B cell reactivity is present in the spleens of mice rendered tolerant by haptenated self, but that Ly-1,2,3 or Ly-1 + Ly-2,3 suppressor T cells prevent their responsiveness.
Antibody-Independent Neutralization of Vesicular Stomatitis Virus by Human Complement
Authors: Mills Bonnie J. , Beebe Deborah P. , Cooper Neil R.
Published: December 2022

Vesicular stomatitis virus (VSV) is efficiently neutralized by normal, nonimmune human serum without the participation of antibody. Neutralization is complement-(C) dependent and requires the early-acting components of the classical pathway, C1, C4, C2, and C3, but not later-acting C components. In further studies, normal human serum was found to markedly increase the density of a variable but significant proportion of virus-associated RNA and to markedly decrease the density of the remainder of virus-associated RNA. The RNA of increased density was found to be dense ribonucleocapsid cores released from VSV by C-dependent viral lysis mediated through the classical pathway. The released ribonucleocapsid cores found at the bottom of sucrose density gradients after incubation of VSV with human serum were resistant to degradation by proteolytic enzymes.

The VSV-derived RNA found floating on the tops of sucrose density gradients performed on serum-treated VSV was infectious virus. The decreased density was due to binding of VSV to human serum lipoproteins (LP), primarily very low density lipoproteins (VLDL). Binding of VLDL to VSV required the presence of the viral envelope and the external glycoprotein, G. Despite the binding of LP to VSV, LP did not neutralize VSV, and LP-depleted sera were fully active in neutralizing VSV. Thus, LP do not represent an accessory factor for the C-dependent neutralization of VSV.
Genetic Control of Experimental Autoimmune Myasthenia Gravis in Mice
Authors: Christadoss Premkumar , Lennon Vanda A. , David Chella
Published: December 2022

As a first step in determining the genetic control of experimental autoimmune myasthenia gravis in mice, we tested the proliferative responses of lymph node cells to torpedo acetylcholine receptors (TAR). Studies with congenic and recombinant inbred strains of mice revealed that T-cell responses to TAR are controlled by an H-2-linked Ir gene, mapping in the I-A subregion of mouse major histocompatibility complex.
Cell-Mediated Cytotoxic Responses of Spleen Cells from Mice Bearing Primary, Chemically Induced Tumors
Authors: Civin Curt I. , Dorfman Nikolay , Eggers Arnold , Fink Kenneth , Penvose Douglas , Hsu C. K. , Wunderlich John R.
Published: December 2022

Sarcomas were induced in C57BL/6 mice by using 3-methylcholanthrene. Spleen cells taken from these mice bearing primary, chemically induced tumors and from matched control mice were assessed for the capacity to generate cell-mediated cytotoxic cell activity after in vitro sensitization. Spleen cells from tumor-bearing mice generated strong cell-mediated cytotoxic responses against alloantigens and antigens on syngeneic cells.
Lipid A from Endotoxin: Antigenic Activities of Purified Fractions in Liposomes
Authors: Banerji Benoy , Alving Carl R.
Published: December 2022

Isolation of lipid A by acid hydrolysis of Shigella flexneri lipopolysaccharide resulted in a product that consisted of a heterogeneous mixture of bands when visualized by thin layer chromatography. Differential extraction with ethyl acetate and chloroform, or extraction with EDTA, followed by chloroform-methanol-water (Bligh-Dyer extraction), or a combination of both extraction schemes, resulted in partial purification of immunologically active lipid A. Eight fractions were purified further by preparative thin layer chromatography, and each of the fractions had phosphate, carbohydrate, and esterified fatty acids. Upon incorporation into liposomes, five of the eight purified fractions reacted with anti-lipid A serum, but the three fractions with the most number of esterified fatty acids failed to react with anti-lipid A serum. At least one fraction that originally was unreactive with anti-lipid A serum became reactive as a hapten inhibitor upon removal of esterified fatty acids by alkaline hydrolysis. Alkali-treated fractions from “unreactive” and “reactive” lipid A had similar activities as hapten inhibitors. Our data suggest that lipid A can exist in multiple forms that differ by the number and placement, and possibly by the type, of fatty acids linked to the carbohydrate of lipid A. Highly acylated forms of lipid A do not react with antiserum against the unpurified lipid A mixture, but removal of fatty acids does expose immunoreactive groups.
Lyt Phenotypes of Responding Cells in Secondary Alloantigen Responses
Authors: Alter Barbara J. , Bach Fritz H.
Published: December 2022

Lymphocytes responding in a “secondary” MLC-CML system, after in vitro sensitization, apparently fall into two classes with regard to their Lyt phenotype. First, are the cells that form the majority of the proliferating cells after restimulation with either I or K + I differences, which are Lyt 1-2-, and second, are Tc that are Lyt 1-2+. The Lyt 1-2- proliferating cells are not cytotoxic and are lysed by treatment with anti-Thy 1.2 serum in the presence of C.
The Murine Kupffer Cell
Authors: Richman Lee K. , Klingenstein R. James , Richman Jill A. , Strober Warren , Berzofsky Jay A.
Published: December 2022

Murine Kupffer cells, the tissue macrohages of the liver, were isolated by collagenase digestion, differential sedimentation over Metrizamide, and glass adherence. The resultant cell population was more than 86% phagocytic, and 95% of cell stained positively for α-naphtyl butyratc esterase activity. The cells also had cell surface receptors for complement (C) and the Fc portion of IgG. In additon, a large proportion of Kupffer cells was shown to bear Ia antigens: about half of the cells bore I-A subregion-encoded antigens. Kupffer cell populations were capable of reconstituting antigen-stumulated proliferative responses of antigen-primed, macrophage-depleted, lymph node T cells. The ability to reconstitute proliferation was enriched in the adheren population and was resistant to radiation and treatment with an anti-Thy antiserum and C.

We conclude that isolated murine Kupffer cells bear the Ia phenotype of accessory cells that function in antigen presentation and that Kupffer cells can paricipate in the induction of antigen-specific immune responses. These data suggest that Kupffer cells may play a role in modulating responses to enterically derived antigens.
Relationship Between Fc (IgG) Receptors and Alloantigens on the Surface of BALB/c B Cell Lymphoma Lines
Authors: Kanellopoulos-Langevin Colette , Jin Kim K. , Sachs David H. , Asofsky Richard
Published: December 2022

From a panel of spontaneous BALB/c lymphoma lines with B cell characteristics, including Ia antigens and receptors for the Fc portion of IgG (Fc(IgG)), three cell lines were selected for further study of the possible relationships between Fc (IgG) receptors, H-2D, Ia, and Mls-associated LyM antigens on their surface. We have found that Fc (IgG) binding, assayed by sheep or ox erythrocyte-antibody (EA) rosetting, could be inhibited by polyvalent anti-Ia sera on Ia positive (Ia+) cell lines (A20, K46). Antisera directed against antigens coded by individual I-subregions also inhibited EA rosettes. No comparable inhibition of Fc receptors was observed on a cell line (M12) that had no detectable Ia antigens on the cell surface. LyM antigens were detected on all cell lines, and all lines (Ia+ or Ia-) could be inhibited with antisera directed against LyM antigens. From the results obtained with the M12 cell line, we can conclude that Ia antigens are not mandatory on the cell surface for Fc (IgG) receptors to be functional or to be blocked. Anti-H-2D sera were also inhibitory in all cases although on two cell lines (A20, M12) the pattern of inhibition was clearly different from that produced by anti-Ia or anti-LyM sera. The differences we have observed in B cell marker interactions among these cell lines may reflect their origin from different distinct B cell subpopulations.
Expression of a Sheep Red Blood Cell Receptor by a Murine Lymphoma
Authors: Callahan Gerald N. , Pellegrino Michele A. , Ferrone Soldano , Haubrich Linda , Reisfeld Ralph A.
Published: December 2022

Murine 6C3HED lymphoma cells were found to rosette with sheep red blood cells (SRBC). Normal C3H lymphocytes did not exhibit this property. This rosetting capacity of 6C3HED cells was found to be an accurate and reproducible means for discriminating between normal and tumor cells. The SRBC receptor on these lymphoma cells appeared to be serologically distinct from that expressed by normal human T lymphocytes since reciprocal blocking experiments demonstrated that inhibitory antisera were not cross-reactive. The expression of the SRBC receptor by the 6C3HED cells appeared to correlate with the expression of a tumor-associated antigen and was spatially related to an antigen expressed by 6C3HED and normal neonatal but not adult mouse cells.
Generation of Biologic Activity from the Purified α-Chain of C5
Authors: Phan Sem H. , Ward Peter A.
Published: December 2022

The α- and β-chains of the fifth component of human complement (C5) have been isolated and their physical and biologic properties have been characterized. After electrophoresis in SDS-poly-acrylamide slab gels, the chains were eluted from the gels and extensively dialyzed. The amino acid composition of each chain was then determined. On SDS-gels, the α-chain was PAS positive whereas the β-chain revealed little or no staining. As a measure of chemotactic activity, the lysosomal enzyme-releasing activity of both chains was examined before and after trypsinization; activity resided almost entirely in the α subunit. Reconstitution of C5 from its isolated chains, followed by trypsinization resulted in slightly less activity than that from the individual α subunit. These findings provide direct support for previous evidence suggesting the biologic activity for neutrophils derives entirely from the α subunit of C5. This represents the first report of direct recovery of biologic activity from a purified subunit chain of C5.
Antigen Specific T Cell-Mediated Suppression
Authors: Pierres M. , Benacerraf B. , Germain R. N.
Published: December 2022

In nonresponder (NR) mice bearing the H-2p, q, s haplotypes, in vivo priming with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) leads to a predominant suppressor T cell (Ts) response. Cell-free extracts obtained by sonication of such GAT-Ts contain a material(s) (GAT-TsE) that suppresses the GAT-specific plaque-forming cell (PFC) response to the immunogenic complex GAT-methylated bovine serum albumin (GAT-MBSA) in syngeneic or allogeneic NR strains. In contrast, GAT-TsE fails to directly suppress the anti-GAT PFC response of various responder (R) strains. We have recently described experimental conditions that allow the in vitro generation of GAT-Ts by using R spleen cells. We now report that culture supernatants of such in vitro induced GAT-Ts, generated in the absence of appropriate macrophage antigen presentation, contain a T cell-derived suppressive material (GAT-TsF) that 1) acts without apparent genetic restriction on the primary in vitro GAT PFC response of R and NR mice, 2) binds specifically to antigen (GAT), and 3) bears determinants coded for by the I-J subregion of the H-2 complex. In addition, coculture of R spleen cells with in vitro derived GAT-TsF leads to the induction of new GAT-Ts (Ts2) able to suppress syngeneic primary GAT PFC responses in vitro. These observations provide insight into the means by which GAT-Ts regulate GAT responses in R mice, as well as raise questions concerning the relationship between GAT-TsE and GAT-TsF.
Membrane Orientation and Location of Multiple and Distinct Allotypic Determinants of Mouse Lymphocyte IgD
Authors: Kessler Steven W. , Woods Virgil L. , Finkelman Fred D. , Scher Irwin
Published: December 2022

The general structure, surface orientation, and location of allotypic determinants of mouse lymphocyte IgD have been deduced by enzymatic and immunochemical dissection of this molecule on the cell membrane. After limited trypsin digestion of IgD of the a (and cross-reacting c) and b allotypes, IgD was no longer detectable on cell surfaces by immunofluorescent staining with an antiserum against light chain determinants, an allotype specific heteroantiserum against IgDa, and a hybridoma antibody specific for the IgDb allotype. Immunoprecipitations performed with these reagents and m.w. analyses by polyacrylamide gel electrophoresis in sodium dodecyl sulfate, after lactoperoxidase-catalyzed cell radioiodination and trypsin digestion, indicated that the respective cleavage fragments were contained in the incubation medium and corresponded to the Fab portion of IgD. On the other hand, trypsin digestion reduced, but did not eliminate immunofluorescent staining with a heteroantiserum that bound IgD determinants common to all allotypes, and straining with two other hybridoma antibodies specific for the a and b allotypes of IgD was only minimally affected. Immunoprecipitations with these reagents indicated that the respective antigenic fragments, corresponding to the Fc portion of IgD, were retained on the cell membrane. Therefore, mouse lymphocyte IgD contains distinct allotypic determinants on both the Fab and Fc portions. Furthermore, it was determined that both fragments bore carbohydrate moieties by lentil lectin chromatography, and that cleavage took place NH2-terminal to a disulfide bond joining the two heavy chains in the Fc region. These findings point to a high degree of structural homology between mouse membrane IgD and human IgD myeloma proteins.
Functional Characterization of Mouse Lymphocyte Subpopulations Identified by Their Natural Binding of Bacteria
Authors: Chen Wen-Yuan , Teodorescu Marius , Mayer Eugene P.
Published: December 2022

Three mouse B cell subpopulations (B1, B2 and B3) can be identified by their natural binding of bacteria. To determine whether these subpopulations have unique functions, we assayed the number of anti-SRBC-secreting cells and the number of Ig-secreting cells in unseparated populations and in populations in which the B2 and B3 cells were removed by immobilized monolayers of Escherichia coli-2, a bacteria that binds B2 and B3 cells. Essentially all of the plaque-forming cells present in the unseparated population were found in the B1-enriched population, suggesting that most of the antibody-secreting and Ig-secreting cells were in the B1 subpopulation. To show conclusively that the anti-SRBC-secreting cells resided in the B1 subpopulation, the Jerne plaque assay was performed on slides by using lymphocytes prelabeled with various bacteria and the cells that gave rise to the plaques were directly examined. Essentially all of the secreting cells were labeled with Corynebacterium xerosis, which binds to the B1 and B2 cells, whereas very few of the secreting cells were labeled with Arizona hinshawii, which binds to the B2 cells, or with Escherichia coli-2, which binds to the B2 and B3 cells. Thus, the B1 subpopulation contained essentially all of the antibody-secreting cells, which indicates that the B cell subpopulations identified by bacteria are functionally different.
Autoimmune Reactions Against Liver Cells by Syngeneic Neuraminidase-Treated Lymphocytes
Authors: Kolb-Bachofen Victoria , Kolb Hubert
Published: December 2022

We have found that the entrapment of neuraminidase-treated lymphocytes in the liver leads to the induction of autoimmune cellular cytotoxic reactions.

Lymphocytes from mouse spleen and thymus were incubated with neuraminidase in vitro and injected i.v. into syngeneic recipients. Lymphocytic infiltrations into the liver were seen 7 days later with both types of cells. After repeated weekly injections of asialo-lymphocytes, destruction of liver tissue became apparent. Electronmicroscopic studies showed that hepatocytes, fat storage cells, and endothelial cells were affected, mainly at the hepatic periphery.

It is concluded that the adhesion of asialo-lymphocytes to liver cells induces their cytotoxic activity. Similar reactions may occur after paramyxovirus infection due to the action of viral neuraminidase.
Immunopotentiating Effects of Amphotericin B
Authors: Shirley Sandra F. , Little J. Russell
Published: December 2022

Contact sensitivity responses to dinitrofluorobenzene (DNFB) or oxazolone were enhanced by amphotericin B (AmB) administration. This adjuvant effect of AmB was documented in mice by ear thickness measurements, ear histology, and the 5-iodo-2′-deoxyuridine-125I ear assay. The optimum immunopotentiating effect of AmB required its simultaneous administration at the time of skin sensitization. AmB-induced adjuvant effects were also observed in adoptive transfer experiments in which syngeneic recipients of lymph node cells from animals sensitized with DNFB plus AmB gave stronger contact sensitivity responses than recipients of cells from mice sensitized with DNFB alone. AmB also interfered with tolerance induction by i.v. dinitrobenzene sulfonic acid, suggesting that its adjuvant effects involve inhibition of suppressor cells or their precursors.
Immunopotentiating Effects of Amphotericin B
Authors: Shirley Sandra F. , Little J. Russell
Published: December 2022

Enhanced in vitro proliferative responses to DNBSO3 were seen in lymph node cells and spleen cells after in vivo sensitization of mice with DNFB plus AmB compared with mice primed with DNFB alone. The T cell proliferation in the nylon column nonadherent fraction for both groups was highly similar, and the enhanced lymph node cell proliferation with AmB was demonstrated to be in the nylon adherent population consisting of both T and B cells.

These and earlier studies of immunopotentiation by AmB are consistent with a mechanism that depends on selective interaction of the polyene with a subset of T cells and a resultant impairment of the normally induced suppressor regulation that limits the magnitude and duration of immune responses.
Natural Killing in Estrogen-Treated Mice Responds Poorly to Poly I·C Despite Normal Stimulation of Circulating Interferon
Authors: Seaman William E. , Merigan Thomas C. , Talal Norman
Published: December 2022

Natural killing by mouse spleen cells can be stimulated in vivo by interferon or by agents that stimulate interferon, such as poly I·C. Natural killing can be suppressed in vivo by the sustained administration of 17β-estradiol. In BALB/c mice that had been treated with 17β-estradiol for 10 weeks, natural killing did not respond to intravenous poly I·C, although stimulation of circulating interferon was equal to controls. Estradiol, then, does not block interferon production but does suppress the response of natural killer cells to interferon. It is suggested that estrogens either block the maturation of natural killer cells or reduce the number of natural killer cell precursors.
Human Cell Membrane Components Dominant in T Cell Lineage: Identification and Characterization of Human TL-Like Antigens
Authors: Tanigaki Nobuyuki , Tokuyama Haruhiko , Fukunishi Tokanobu , Minowada Jun , Pressman David
Published: December 2022

Cell membrane components that contain β2-microglobulin were purified from cells of a human T cell-type leukemia cell line, HPB-ALL. They contained membrane components that have the same molecular size and the same subunit structure as HLA(A,B,C) antigens but are separable from the typical β2-microglobulin-containing cell membrane components, i.e., the HLA(A,B,C) antigens, by xenoantibody reagents. A sensitive radioimmunoassay was constructed for detection of the T cell membrane components. The assay revealed that the cell membrane components are expressed exclusively on cells of T cell-type leukemia cell lines among the human lymphoid cell lines tested, predominantly in thymus, among the human organs and tissues tested. They were not present on cells of human B cell-type cell lines or on cells of nonlymphoid organs and tissues. No alloantibodies directed to the T cell membrane components, the putative human homologues of mouse TL antigens, were found in any of the human tissue typing sera tested.
Stimulation of the in vivo dinitrophenyl antibody response to the DNP conjugate of L-glutamic acid60-L-alanine30-L-Tyrosine10 (GAT) polymer by a synthetic adjuvant, muramyl dipeptide (MDP): target cells for adjuvant activity and isotypic pattern of MDP-stimulated response.
Authors: Lowy I , Theze J , Chedid L
Published: December 2022

Specific anti-dinitrophenyl (DNP) response to DNP-conjugated L-glutamine60-L-alanine30-L-tyrosine10 (DNP-GAT) was obtained in GAT-responder mice by using synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) as adjuvant. Significant levels of anti-DNP antibodies were observed during a secondary response to DNP-GAT, when both antigen and MDP were used for priming. In this system, MDP was able to prime the carrier-specific T cells but not the hapten specific B cells. The study of the isotypic pattern of the anti-DNP response shows that MDP stimulates only the appearance of specific anti-DNP IgG1 plaque-forming cells. Anti-DNP plaque-forming cells were stimulated in animals primed with DNP-GAT in Freund's complete adjuvant or in Maalox-pertussis and used as control IgG1, IgG2a, and IgG2b.
Inhibition of mitogen-induced polyclonal activation by by a synthetic adjuvant, muramyl dipeptide (MDP).
Authors: Löwy I , Leclerc C , Bourgeois E , Chedid L
Published: December 2022

A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), was previously shown to enhance polyclonal antibody response in murine spleen cell cultures. When MDP was added to the culture together with a potent murine B cell mitogen (such as bacterial lipopolysaccharide (LPS)), it inhibited completely the LPS-induced polyclonal activation without affecting either the 3H-thymidine incorporation or the number of blast cells in cultures. Strong suppression of mitogen-induced polyclonal activation by MDP was obtained by using a large range of cell concentrations in cultures and over various dosage levels of the stimulating mitogens (LPS and NWSM). An inhibition could be obtained even when MDP was added 24 hr after the addition of the mitogen, and highly significant suppression was observed in the absence of cell division in the cultures.
Physical properties of cytomegalorvirus immune complexes prepared with IgG neutralizing antibody, anti-IgG, and complement.
Authors: Rundell B B , Betts R F
Published: December 2022

Human cytomegalovirus (CMV) strain AD 169 was reacted with IgG antibody (ab) from a CMV-infected renal transplant patient. A portion of he virus was neutralized, but infectious CMV-ab complexes that could be neutralized by adding rabbit anti-human IgG (A-IgG) or complement (C) were also generated. The immune complexes were examined, and the following observations were made: 1) CMV ab sufficient to cause 94% neutralization did not induce measurable changes in virion size or density. 2) The CMV-ab complexes increased slightly in size after reaction with A-IgG. 3) C increased the size and density of CMV-ab complexes to a greater degree than A-IgG. Virus aggregation did not occur with ab alone or with ab + A-IgG. However, clumping may have occurred in the presence of ab + C. 4) C also damaged virus envelopes, rendering viral DNA sensitive to DNase. 5) CMV-ab complexes absorbed to host cells as efficiently as native CMV. A-IgG or C partially inhibited complex attachment to the cells and increased the rate of release of cell-attached CMV. These findings suggest that virus neutralization may occur in a multistage process by more than one mechanism depending on the immune reagents employed. The physical changes in virus particles caused by A-IgG or C may be contributing factors in the neutralization process.
Surface markers of a purified peritoneal eosinophil population from Mesocestoides corti-infected BALB/c male mice.
Authors: Hogarth P M , Cruise K M , McKenzie I F , Mitchell G F
Published: December 2022

Eosinophils of approximately 95% purity were prepared from the peritoneal cavities of BALB/c male mice infected with larval cestode, Mesocestoides corti. The alloantigenic surface marker phenotype of this cell population was shown to be H-2+Ly4+Ly5+Lyt-1-,2-,3-Ly-6-,7-Ia-Thy-1-TL-. Two of four anti-Lyt-2 sera were positive when tested on purified eosinophils by using the Staphylococcus aureus protein A sheep erythrocyte rosetting method, but absorption studies indicated that this reaction was not due to anti-Lyt-2 antibodies. Eosinophils are therefore Lyt-2-, although some Lyt-2 sera contain additional eosinophil reactive antibodies. A proportion (20 to 40%) of the population of eosinophils was positive for the Fc receptor, but all were negative for the C3 receptor and for surface immunoglobulin.
Restriction of antigen recognition in mouse B lymphocytes by genes mapping within the major histocompatibility complex.
Authors: Gorczynski R M , Kennedy M J , MacRae S , Steele E J , Cunningham A J
Published: December 2022

B cells, like T cells, show genetic restrictions in their interactions with other cells. B cells from (C3H/HeJ X C57BL/6J)F1 mice were stimulated with foreign antigen (sheep erythrocytes, SRBC) in parental-strain irradiated hosts. They could be subsequently activated to antibody formation in vitro by SRBC presented on cells of the same parental type, and much less by SRBC on cells of the other parental type. The restriction was seen whether antigen was presented on macrophages or by activated T cells. Experiments with congenic mice showed that the restriction was controlled by the MHC locus. Restriction of F1 B cells to responsiveness against either parental haplotype was much more readily induced in bone marrow than in splenic populations. This restriction could be broken down by giving the irradiated host a second injection of antigen 3 weeks after the first; this probably reflects "reeducation" of the F1 B cells by SRBC associated with donor, F1-type macrophages. Normal unprimed spleen B cells also showed a strong preference for activation by SRBC in association with syngeneic activated T cells.
Characterization of in vitro T lymphocyte colonies from normal mouse spleen cells: colonies containing cytotoxic lymphocyte precursors.
Authors: Ching L M , Miller R G
Published: December 2022

The functional activity of T cell colonies grown from normal murine spleen cells has been examined. Up to 75% of the T cell colonies contain cytotoxic lymphocyte precursors (CLP). One out of three colonies contains CLP, which can respond to a given foreign H-2 haplotype. The CLP from the T cell colonies appear identical to the CLP in lymph node tissues in their degree of cross-reactivity and requirement for accessory cells. The effector cells produced were shown to be T lymphocytes. Karyotypic analysis of the cells in colonies grown from a mixture of T6-marked and normal spleen cells indicated that individual colonies were formed from an initial small aggregate of cells. Radiation survival data indicated that the colony-forming unit contains three or fewer proliferating cells.
Cyclic AMP modulation of Fc receptor expression on a pre-B cell lymphoma.
Authors: Burchiel S W , Warner N L
Published: December 2022

Cyclic AMP-elevating agents have been shown to increase the expression of Fc receptors on the Abelson virus-induced pre-B cell tumor ABE-8. Such agents included isoproterenol, PGE1, 3-isobutyl-1-methyl xanthine, and 8 BrcAMP. The positive inductive effect produced by these agents was inhibited by 8 BrcGMP and PGF2 alpha, which putatively elevate cyclic GMP levels. Other agents also shown to induce Fc receptor expression were LPS and certain batches of fetal calf sera. In contrast to the inductive effect produced by cyclic AMP elevating agents, 8 BrcGMP and PGF2 alpha were unable to reverse the increased Fc receptor expression produced by LPS and fetal calf sera. Thus, these latter agents may act via a qualitatively different mechanism in producing a change in phenotypic expression. The results of this study are discussed in terms of the use of tumor cells as a model system for studying the pharmacologic control of lymphocyte differentiation.
Lymphocyte function in experimental African trypanosomiasis. III. Loss of lymph node cell responsiveness.
Authors: Wellhausen S R , Mansfield J M
Published: December 2022

The relationship between immunosuppression and suppressor cell activity in the lymphoid organs of animals with experimental African trypanosomiasis has been examined further. In the present study we measure the primary in vitro PFC response to SRBC by spleen and lymph node cells from Trypanosoma rhodesiense infected or drug-cured C57BL/6 mice. Passive transfer experiments with this culture system tested for the presence or absence of suppressor cells. We demonstrate that infected mice exhibit immunosuppression in the spleen cell population several weeks before becoming suppressed at the level of the lymph node cell populations. Although suppressor cells are present in immunosuppressed spleen cell populations, suppression of lymph node cell responsiveness was not attributable to suppressor cells detectable withi, lymph nodes. After Berenil treatment of terminally infected mice immunocompetence was restored gradually, first to the lymph node cells and subsequently to the spleen cell population. Recovery of spleen cell responsiveness was attributable to the loss of detectable suppressor cell activity within spleens. These results demonstrate that there is anatomical restriction of the suppressor cell population to trypanosome-infected mouse spleen and that loss of immunocompetence in the lymph nodes may be due to factors unrelated to suppressor cell effects.
Interactions among rheumatoid synovial cells and monocyte-macrophages: production of collagenase-stimulating factor by human monocytes exposed to concanavalin A or immunoglobulin Fc fragments.
Authors: Dayer J M , Passwell J H , Schneeberger E E , Krane S M
Published: December 2022

Adherent synovial cells (ASC) were obtained from minced synovium from patients with rheumatoid arthritis by dissociating the lining cells from the extracellular matrix and dispersing them with proteases. These cells produce high levels of latent collagenase in primary culture. With passage of ASC, collagenase levels decrease but can be stimulated by a soluble factor (MCF) released in vitro from cultured human blood monocyte-macrophages. Monocyte cultures exposed to aggregated immunoglobulin, Fc fragments of immunoglobulin or concanavalin A (Con A) increase production of MCF several-fold more than the control cultures. MCF production by monocytes exposed to Fab fragments does not differ from controls. Although aggregated immunoglobulin, Fc fragments, and Con A stimulate PGE2 synthesis and secretion by human monocytes, the effects on MCF production are not mediated by PGE2 since concentrations of indomethacin that completely block PGE2 production do not inhibit MCF production. These findings of increased production of MCF by monocytes in response to substances that probably exert their effects via surface receptors could be relevant in interpreting the in vivo role of immune complexes in diseases associated with connective tissue destruction.
Inhibition of DRw antisera reactivity by mono and oligosaccharides.
Authors: Mann D L , Muchmore A
Published: December 2022

Mono and oligosaccharides were used to inhibit the cytotoxicity of antisera detecting HLA-DRw antigens on monocytes isolated from peripheral blood. Certain sugars preferentially inhibited antisera detecting some DRw antigens and not others. Sera detecting HLA-A and B antigens were not inhibited with the sugars used. Anti-DRw sera blocked the attachment of radiolabeled sugars to monocytes with the same patterns as the reciprocal blocking of cytotoxicity by the sugars. The results were not consistent with the intrepretation that carbohydrates are an antigenic "component" of DRw specificity, but rather that the surface structures, possibly those bearing the DRw antigens, are receptors for mono and oligo saccharides.
The LEW.BN(2R) strain: a recombinant in the rat MHC.
Authors: Lynch D H , DeWitt C W
Published: December 2022

Cell-mediated cytolytic (CMC) responses resulting from immunizations between rat strains considered to be RT1 (Ag-B) identical (LEW.B3:BN) are capable of detecting a membrane determinant(s) controlled by a locus linked to RT1, which has been designated Ag-L. The Ag-L gene region has been isolated in a recombinant line, tentatively designated as LEW.BN(2R), and has been assigned the RT1r5 haplotype. The data presented demonstrate that the genes responsible for MLR stimulation in the 2R strain are of LEW origin. In addition, LEW.B3 anti-BN CTL appear to recognize multiple specificities, only one of which is in the 2R strain. Some of the remaining specificities in BN may be the result of interactions between undetected genes that have been separated in the LEW.B3 and 2R strains.
Interferon enhances the expression of Fc gamma receptors.
Authors: Fridman W H , Gresser I , Bandu M T , Aguet M , Neauport-Sautes C
Published: December 2022

Murine T2D4 cells derived from a T cell hybrid line were incubated with partially purified or electrophoretically pure mouse interferon and tested for the expression of Fc gamma R as assessed by a) counting the number of cells forming rosettes with IgG-sensitized sheep erythrocytes, and b) incubating the cells with heat-aggregated rabbit IgG and then determining either the number of cells stained with fluorescein conjugated goat anti-rabbit IgG or the extent of labeling by using radioactive iodinated staphylococcus protein A. Although interferon induced a rapid increase in Fc gamma R expression on the Fc gamma R-positive T2D4 cells, it did not induce either Fc gamma R on the Fc gamma R negative BW5147 cells or Fc gamma R on either cell line. Human leukocyte interferon enhanced the expression of Fc gamma R on human Burkitt cells (Daudi) but did not affect the expression of Fc gamma R on mouse cells. We suggest that interferon may influence several effector functions of the immune system by modulating Fc receptor expression.
Effect of the 5-hydroperoxide of eicosatetraenoic acid and inhibitors of the lipoxygenase pathway on the formation of slow reacting substance by rat basophilic leukemia cells; direct evidence that slow reacting substance is a product of the lipoxygenase pathway.
Authors: Falkenhein S F , MacDonald H , Huber M M , Koch D , Parker C W
Published: December 2022

Previous studies in a line of rat basophilic leukemia (RBL 1) cells have indicated that the slow reacting substance (SRS) made during stimulation with the divalent cation ionophore, A23187, is derived from arachidonic acid (AA). In the present report, various inhibitors of AA metabolism were compared with regard to their effects on SRS formation and incorporation of radioactivity from [1-14C]-AA into known metabolites of the lipoxygenase and cyclooxygenase pathways. An apparently close parallel between lipoxygenase product formation and SRS synthesis is demonstrated. In addition, exogenous 5-hydroperoxy-eicosatetraenoic acid (5-HPETE) has been shown to markedly enhance SRS synthesis, even when A23187 is absent. The data provide very strong evidence that SRS is produced through the lipoxygenase pathway.
Induction of suppressor T cells of antibody formation under conditions that preferentially stimulate DTH.
Authors: Ramshaw I A , Woodsworth M , Wright K , McKenzie I F
Published: December 2022

These studies describe the conditions under which antibody-forming cells and TDTH cells are selectively induced in vitro. TDTH cells are preferentially stimulated when high doses of antigen are included in the culture. Antibody-forming cells, on the other hand, are optimally stimulated with a 100 to 1000-fold less concentration of antigen. The conditions that optimally stimulate TDTH cells also induce a population of suppressor T cells that inhibit the antibody response. However, although their inductive requirements are similar, the suppressor T cells of antibody formation are a distinct subpopulation of cells from the TDTH cells. Whereas the suppressor T cells are LY-1-, 2+, 4-, 6+, and Ia+; the TDTH cells are Ly-1+, 2+/-, 4-, 6+, and Ia-. Furthermore, the DTH cells are sensitive to high doses of irradiation, whereas the suppressor cells are resistant. Based on the Ly phenotype and the kinetics of suppression, the suppressor T cells are not the "feedback suppressors" that have been identified in other systems. The system described in this paper provides a means whereby the cells that regulate humoral and CMI can be studied in vitro.
Genetic mapping of an H-2-associated antigen expressed on regulatory T cells.
Authors: Plate J M
Published: December 2022

T lymphocytes that serve regulatory functions in the generation of effector T cells to alloantigen and to altered syngeneic cells express a distinguishing H-2-associated cell surface marker that we have termed Ha. Genetic mapping studies with the B10.A(2R), B10.A(4R), B10.A(5R), and LG/Ckc lines of mice have delineated the locus determining the expression of Ha to the right of H-2K and left of H-2IB or within the I-A region. Thus these regulatory T lymphocytes express Ia antigens.
A polymorphism of the gamma-chain of mouse C4 controlled by the S region of the major histocompatibility complex.
Authors: Ferreira A , Michaelson J , Nussenzweig V
Published: December 2022

Three phenotypes of the gamma-chain of mouse C4 have been detected by a modification of the two-dimensional O'Farrell technique. Strains carrying the H-2s, H-2p, H-2f and H-2ja haplotypes had chains with pI 7.4 (gamma 1). Strains with H-2k, H-2q, H-2d, H-2r, H-2b, H-2u, and H-2w7 had gamma-chains with pI 6.9 (gamma 2), and strains carrying a wild-derived haplotype had gamma chains with pI 6.5 (gamma 3). The genes controlling this polymorphism were mapped in the S region of the H-2 complex by using congenic strains.
Evidence that specific oligosaccharides block early events necessary for the expression of antigen-specific proliferation by human lymphocytes.
Authors: Muchmore A V , Decker J M , Blaese R M
Published: December 2022

We have previously shown that monosaccharides and disaccharides will block the expression of spontneous monocyte-mediated cytotoxicity. Our data were consistent with the hypothesis that human mononuclear cells express lectin-like receptors that are capable of binding to a variety sugar moieties found on target cell membranes. In this communication, we will present evidence that monosaccharides and disaccharides are also capable of blocking the expression of T cell reactivity as measured by an in vitro antigen-specific proliferative assay. The majority of sugars that blocked monocyte-mediated cytotoxicity had no effect on antigen-specific proliferation. Those sugars that did suppress antigen-induced proliferation had no effect on PHA-induced proliferation. Furthermore, some of these sugars only inhibited if they were added at the initiation of the assay; they failed to inhibit if added 24 hr after the initiation of the assay. Antigen-pulsing experiments suggested that these sugars did not block antigen uptake by human monocytes. These data suggest that a variety of cellular interactions may be mediated by receptors with specificity for simple sugars. The ability to block these naturally occurring lectins specifically both in vitro and in vivo may prove to be a powerful tool for dissecting out various forms of cellular recognition and collaboration.
Changes in macrophage ectoenzymes associated with anti-tumor activity.
Authors: Morahan P S , Edelson P J , Gass K
Published: December 2022

The phenotype of three ectoenzymes was determined for murine resident peritoneal macrophages, macrophages elicited in vivo by treatment of mice with thioglycollate, Corynebacterium parvum or pyran, and for resident macrophages activated in vitro by treatment with lymphokine. The relationship of these biochemical markers to macrophage antiviral and anti-tumor activity was established. Thioglycollate-elicited macrophages showed a unique ectoenzyme phenotype, with increased leucine aminopeptidase and alkaline phosphodiesterase I activity and markedly reduced 5'-nucleotidase activity as compared with resident macrophages. Thioglycollate-elicited macrophages exhibited extrinsic antiviral activity against herpes simplex virus but did not show anti-tumor activity. Another ectoenzyme phenotype was shared by macrophages elicited in vivo by treatment of mice with the immunomodulators or in vitro by treatment with antigen-specific lymphokine. These macrophage populations showed increased levels of leucine aminopeptidase but reduced levels of both 5'-nucleotidase and alkaline phosphodiesterase. This ectoenzyme phenotype was associated with the acquisition by the macrophages of selective anti-tumor activity. There appear to be clear distinctions in biochemical markers and functional properties among macrophages activated by different mechanisms.
Analysis of NZB hyperdiploid spleen cells.
Authors: Raveche E S , Alabaster O , Tjio J H , Taurog J , Steinberg A D
Published: December 2022

In order to study the cell types involved in the hyperdiploidy characteristic of NZB mice, flow cytometric techniques, which measure te DNA content of individual cells, have been used together with standard cytogenetic analysis. The aneuploid cells present in NZB mice were found to be clonally derived. These cells were of large size relative to nonaneuploid cells. They could not be removed by lysis with anti-Thy 1 plus complement nor were they present in the nylon-wool column nonadherent fraction, both of which are characteristic of T cells. By further cytotoxic analysis, the aneuploid cells were found not to express Ly-5 nor NK surface antigens, found on natural killer cells. The aneuploid cells had increased quantities of cell surface H-2 antigen. This marked susceptibility to lysis with anti-H-2 serum was associated with one or more extra copies of chromosome 17, which carries the H-2 complex. A large proportion of these cells also expressed surface Ia and Ig. The aneuploid cells found in the spleens of older NZB mice derive from bone marrow stem cells. Neonatally thymectomized and lethally irradiated NZB X DBA/2 recipients of anti-Thy-1 treated young NZB bone marrow cells ultimately developed aneuploid spleen cells. Such cells are not found in intact or thymectomized NZB Z DBA/2 mice nor in recipients of DBA/2 marrow. Finally, congenic NZB mice carrying the CBZ/N xid failed to develop aneuploidy. Taken together, these studies suggest that the aneuploid cell is a bone marrow-derived stem cell destined to differentiate into the B cell subset lacking in CBA/N mice.
The effect of growth hormone and insulin upon MLC responses and the generation of cytotoxic lymphocytes.
Authors: Snow E C , Feldbush T L , Oaks J A
Published: December 2022

The ability of growth hormone (GH) and insulin to influence positively T lymphocytes responding to an alloantigen stimulus in vitro was analyzed through the use of a serum substitute system. The presence of insulin but not GH, enables the generation of a successful mixed lymphocyte culture (MLC) blastogenic response. However, the presence of GH during a 5-day MLC allowed for the generation of cytotoxic T lymphocytes (CTL). It was further demonstrated that GH needed to be present during the first 2 days of the culture system, presumably before the entry of the precursor CTL into cell division. The results are discussed in terms of the induction, by the GH, of ornithine decarboxylase activity and how this might relate to the successful generation of CTL activity.
Immunoglobulins in the cerebrospinal fluid: changes during acute viral encephalitis in mice.
Authors: Griffin D E
Published: December 2022

The development and pathogenesis of immunoglobulin changes in the CSF in acute encephalitis were studied in mice infected with Sindbis virus. Three phases of immunoglobulin changes were noted. 1) During the first 2 days when virus replication in the brain is maximal, few changes were seen in the CSF. 2) At the time of maximal meningeal inflammation, 3 to 5 days after infection, there was a transudation of protein from serum into CSF. 3) During the period of recovery, there was evidence of a local immune response within the CNS. CSF concentrations of all immunoglobulins became increased compared with normal mice and compared with the concentration of albumin, whereas serum immunoglobulin levels remained essentially unchanged. The largest proportionate increase was in IgA. There was no evidence of increased immunoglobulin transfer from serum to CSF by using iodinated immunoglobulins. Comparable amounts of virus-specific IgG and IgA were present in the CSF, whereas serum antibody was primarily IgG. It is concluded that the local immune response to viral encephalitis in mice involves the production of virus-specific IgA as well as IgG.