bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversal by Peritoneal Adherent Cells of Tumor Cell Suppression of T Cell-Mediated Immunity
Authors: Ting Chou-Chik , Rodrigues Dennis
Published: December 2022

Tumor cells and their cell/free products were found to be suppressive for the T cell-mediated cytotoxic response. This was shown by their ability to inhibit the standard mixed lymphocyte culture (MLC) reactions and the failure of these tumor cells to induce cytotoxic response in the allogeneic mixed lymphocyte tumor cell culture (MLTC) reactions. However, this immunosuppressive effect could be completely reversed by the addition of 1 to 10% of syngeneic peritoneal cells (PC) into the MLC or MLTC reactions. Addition of PC not only can reverse the immunosuppression of tumor cells in MLC, but also restores the cytotoxic response to these tumor cells in MLTC. Although PC were needed to restore the cytotoxic response, the cytotoxic effector cells recovered from these cultures were found to be entirely T cells. These PC were needed in the early induction phase of the cytotoxic response. The reversal of immunosuppression can only be obtained when PC were added at the onset of MLTC reactions. Addition of PC at a later time or were left in the effector phase of cytotoxic reactions gave no restoration of the cytotoxic response. In the FBL-3 tumor system, the PC that were responsible for the reversal of the immunosuppression were found to be radioresistant, adherent, Thy. 1-antigen negative, Ia-negative, and Ig-negative. They were also found to be predominantly nonphagocytes. Therefore, they were not typical macrophages. This nonphagocytic population of adherent PC may play a critical role in the regulation of T cell-mediated cytotoxic response to tumor cells.
Antigenic Determinants of Influenza Virus Hemagglutinin
Authors: Russell Robyn J. , Burns William H. , White David O. , Anders E. Margot , Ward Colin W. , Jackson David C.
Published: December 2022

Immunoglobulin G directed against the hemagglutinin (HA) of influenza virus A/Memphis/102/72 (H3N2) was adsorbed with either of two related viruses, A/Port Chalmers/73 (H3N2) or A/Papua New Guinea/75 (H3N2) to fractionate the antibody into “strain-specific” (“specific”) and “cross-reactive” (“common”) populations. These IgG preparations were tested with use of a solidphase radioimmunoassay for their ability to compete with one another in binding to the antigenic determinants of Memphis HA. Their binding avidities were also determined.

It was found that anti-“specific” and anti-“common” IgG preparations competed with each other for the antigenic regions on Memphis HA. In addition, the assignment of anti-HA antibodies to either the anti-“specific” or the anti-“common” category was shown to be completely dependent on the particular virus used for adsorption; the more distantly related the strains being compared, the higher the proportion of antibodies that registered as anti-“specific”, and the higher the average binding avidity of the anti-“specific” antibody population.

It is concluded that so-called anti-“specific” anti-“common” antibodies are directed against the same regions on the HA molecule. This does not necessarily imply that there is only a single antigenic determinant; there may be more than one, each inducing the production of a heterogeneous population of antibody molecules binding with different avidities to that determinant.
Target Cell Recognition by Cytolytic T Cells: Different Requirements for the Formation of Strong Conjugates or for Proceeding to Lysis
Authors: Shortman Ken , Golstein Pierre
Published: December 2022

Conjugates between nonadherent peritoneal exudate lymphocytes from alloimmune mice, and neutral redlabeled or unlabeled tumor cell targets, were assayed by a procedure involving co-sedimentation of lymphocytes and target cells, vigorous resuspension, then visualization under phase-contrast or normal optics. The requirements for obtaining such conjugates, and for maintaining them in a state resistant to shear force, were compared to those for cytolysis in the usual 51Cr release procedure. The following discrepancies were noted between the requirements for formation and visualization of such conjugates, and the requirements for the recognition stage of the cytolytic assay: 1) although in both cases divalent cations were required, more Mg++ was necessary to obtain suspended conjugates than to obtain lysis; 2) although cytochalasin A added before cell contact was inhibitory in both cases, the post-recognition steps leading to lysis were not affected, whereas preformed conjugates were affected; 3) glucose was required to obtain suspended conjugates, whereas the hexose requirement in the 51Cr release assay was restricted to a post-recognition state leading to lysis. The discrepancies between the two assays were explained by the observation that under all the inhibitory conditions tested (addition of EDTA, deoxyglucose, or cytochalasin A) preformed conjugates, although not immediately dissociated, were rendered labile to shear force. The resuspension step, necessary to visualize conjugates, imposed more stringent requirements on the T cell-target cell interaction than did the lytic assay using pelleted cells.

The results suggest that the establishment of a tenacious linke between a cytolytic T lymphocyte and a target cell requires secondary, nonimmunologic interactions that follow the initial specific recognition event, and that these strengthening interactions are not necessary for cytolysis. The T cell receptor itself might only have a weak affinity, or be readily detached from the membrane, so that it has more of a “reading” than a “binding” role. A practical conclusion is that the metabolic requirements for T cell “recognition” are not fixed, but are imposed by the experimental conditions under which recognition is tested.
Genetic Mapping of the Locus Controlling Structural Variations of Murine C3 in the Chromosome 17
Authors: Natsuume-Sakai Shunnosuke , Hayakawa Junichiro , Amano Shigetoyo , Takahashi Morinobu
Published: December 2022

Backcross progeny, (NC × TF/GnLe)F1 × TF/GnLe, was tested for C3 allotype controlled by C3-1 and the expression of mutant gene tf, repeated loss and regrowth of hair. The recombination frequency between these two loci both located in chromosome 17 of the mouse was 24%. Taken together with our previous linkage data, C3-1 is now localized to a position 11 cm more distal than H-2 on chromosome 17.
Macromolecular Insoluble Cold Globulin (MICG): A Novel Protein from Mouse Lymphocytes
Authors: Hauptman Stephen P. , Kansu Emin , Godfrey Scott
Published: December 2022

Macromolecular insoluble cold globulin is a glycoprotein synthesized predominantly by T lymphocytes in the mouse. The present report details experiments demonstrating the plasma membrane distribution of MICG on T lymphocytes. By utilizing immunofluorescent techniques it was shown that MICG was located in the external cell surface of 98% of thymic lymphocytes and 60% of splenic lymphocytes. Furthermore, in spleen cells, it was demonstrated that T cells and not B cells were surface MICG positive. Antibody to MICG was able to cap all of the immunofluorescent-positive (60%) spleen cells. In contrast, anti-MICG antibody did not induce cap formation on thymus cells. Only when dilute solutions of antibody were used did MICG cap on the thymus cells.

Employing limited proteolysis of thymus and spleen cells MICG was shown to be regenerated on the surface of T cells with a half-life of 3.5 hr. The distribution and cell surface characteristics of MICG are discussed in terms of a “receptor-like” function for this protein.
Effect of Specific Phospholipids on the Antibody-Complement-Mediated Killing of Nucleated Cells
Authors: Ohanian Sarkis H. , Schlager Seymour I. , Yamazaki Masatoshi , Ishida Brian
Published: December 2022

Certain phospholipids selectively inhibited or enhanced the cytotoxic action of complement (C) on antibody-coated line-1 and line-10 guinea pig hepatoma cells. Phosphatidylglycerol (PG) inhibited guinea pig, human, goat, and rabbit C but not rat C. Cardiolipin (CL) was effective in inhibiting human and goat C and phosphatidylethanolamine (bovine brain) (PEm) was effective against human, goat, and rabbit C. Phosphatidylethanolamine (egg yolk) (PEegg), phosphatidylethanolamine (E. coli) (PEb) or phosphatidylethanolamine (soybean) (PEsb) were not effective in inhibiting C activity. Phosphatidylserine (PS) was only effective in inhibiting GPC. In contrast, PG enhanced the activity of rat C against line-10 cells sensitized with anti-tumor antibody but not anti-Forssman antibody.

The inhibiting activity was dependent upon the antibody used to sensitize the cells, on the concentration of lipids used to treat the C, and on the time the lipids were added to the C. The inhibitory effect of the lipids appear to be at the stage of formation of T*. Addition of lipids to T* did not interfere with its transformation to dead cells. These results suggest that certain lipids may interfere with fluid-phase activated C components but not bound C components. The role of lipids or lipid-containing macromolecules on C action may be that of providing a hydrophobic environment for an activated C component(s) whereas the fatty acid composition and/or subtle physical properties of individual lipids may influence the functional activity of C.
Frequency of Allogeneic Helper T Cells Responding to Whole H-2 Differences and to an H-2K Difference Alone
Authors: Swain Susan L. , Panfili Peter R. , Dutton Richard W. , Lefkovits Ivan
Published: December 2022

Limiting dilution analysis was used to determine the frequency of splenic T cells that are stimulated by alloantigen to give help in a primary antibody response to SRBC. Serveral haplotype combinations were tested. A semilogarithmic plot of the fraction of nonresponding culture as a function of the number of T cells added to excess B cells gave a straight line intercepting with the origin. Thus a single cell-type was limiting, which was required to help B cells respond to SRBC. The frequency of syngeneic precursors of T helper cells specific for SRBC ranged from 1/10,000 to 1/55,000 with a mean of about 1/20,000. Allohelpers generated by whole H-2 differences gave precursor frequencies that ranged from 1/1000 to 1/7000 with a mean of about 1/2500. Thus allohelpers to whole H-2 differences were approximately 8-fold more frequent than SRBC-specific helpers. When the stimulation was limited to the H-2K difference between the mutant B6.C-H-2ba and wild-type B6, frequencies of from 1/2600 to 1/7900 allohelpers were found with a mean of about 1/5000, approximately half the frequency of allohelpers to whole H-2 differences. Thus some, but probably not all, of the magnitude of allogeneic help can be attributed to the high frequency of helper T cells that respond to a given alloantigen.
Suggestive Evidence for Receptors for Morphine and Methionine-Enkephalin on Normal Human Blood T Lymphocytes
Authors: Wybran Joseph , Appelboom Thierry , Famaey Jean-Pierre , Govaerts André
Published: December 2022

This study reports the in vitro influence of morphine, dextromoramide, levomoramide, and methionine-enkephalin upon normal human T blood lymphocytes by using the active and total rosette tests. Morphine and dextromoramide inhibited the percentage of active T rosettes. This effect was completely reversed in the presence of naloxone, their specific antagonist. The specificity was further demonstrated by the absence of the effect of levomoramide, the inactive enantiomere, upon the rosette system. Methionine-enkephalin increased the percentage of active T rosettes. This effect was specifically inhibited by naloxone. These observations suggest that normal human blood T lymphocytes bear surface receptor-like structures for morphine, dextromoramide, and methionine-enkephalin. Such findings may provide a link between the central nervous system and the immune system.
C3 Deposition in Cholesterol-Induced Atherosclerosis in Rabbits: a Possible Etiologic Role for Complement in Atherogenesis
Authors: Pang Anthony S. D. , Katz Allan , Minta Joe O.
Published: December 2022

Hypercholesterolemia was induced in rabbits by feeding Purina Chow supplemented with cholesterol (5 g/kg body weight/day). The serum cholesterol levels of these rabbits increased progressively and after 3 to 5 months were 4 to 9-fold greater than those of the control animals. Decrease in total hemolytic complement was not apparent during the feeding regimen. Morphologic examination of aortae of these hypercholesterolemic rabbits showed typical atherosclerotic intimal plaques. Immunofluorescent microscopy with fluorescein (F)-labeled anti-rabbit C3 showed deposition of C3 in the intimal and inner medial layers as early as 3 months on high cholesterol diet. C3 deposits were also observed in the renal glomeruli and in the walls of coronary arteries. However, fluorescent studies failed to demonstrate the presence of IgG, IgM, and C4 at these sites. Tissues from control animals fed normal diets were negative for immunoglobulins, C3, and C4. These results suggest that the complement system may be implicated in the pathogenesis of cholesterol-induced atherosclerosis in rabbits.
Adherent Cell Function in Murine T Lymphocyte Antigen Recognition
Authors: Rosenwasser Lanny J. , Rosenthal Alan S.
Published: December 2022

The I region of the MHC appears to control antigen-specific Mø-T lymphocyte interaction. The immune response to antigens such as Glø9 are under control of two distinct I subregions, I-A and I-E/I-C. We have asked in a Mø-dependent, antigen-specific murine T cell proliferation assay whether either or both gene products need be expressed in the antigen-presenting cells. We find that both Ir-Glø9 α and β genes must be expressed and function in the antigen-presenting cell.
Inheritance of Tolerance Susceptibility to Human γ-Globulin in Congenic Mice
Authors: Ranges Gerald E. , Azar Miguel M.
Published: December 2022

The genetic control of susceptibility to tolerance induction with human γ-globulin (HGG) was studied by using H-2 congenic mice. Strains tested that were congenic with C57BL/10Sn were completely tolerized by 1.0 mg deaggregated HGG. In contrast A/Sn mice showed full tolerance whereas A.SW mice were only intermediately tolerant. It was further shown that (B10 × SJL)F1 mice could be rendered tolerant but (B10.S × SJL)F1 mice could not. These data indicate a role for H-2 linked genes in control of tolerance susceptibility. Results obtained with the progeny of (B10.S × SJL)F1 backcrossed to B10.S indicate that two non-H-2 linked genes are involved in control of tolerance induction. Preliminary mapping studies show the H-2 gene located to the left of the IC subregion. These results confirm our previous finding that both H-2 and non-H-2 genes control susceptibility of adult mice to tolerance induction with HGG.
Demonstration and Partial Characterization of 22-nm HBsAg and Dane Particles of Subtype HBsAg/ady
Authors: Hess Georg , Shih J. Wai-Kuo , Arnold Wolfgang , Gerin John L. , Zum Büschenfelde Karl-Hermann Meyer
Published: December 2022

The present paper describes the demonstration of d, y, w, and r HBsAg determinants in one serum. It was shown that there are two populations of HBsAg particles: HBsAg/ad and HBsAg/ady. All complete Dane particles were of subtype HBsAg/ady. Further characterization of HBsAg/ady particles did not reveal morphologic differences when they were compared with HBsAg/ad and HBsAg/ay particles. An HBsAg/ady phenotype may be the result of a double infection with hepatitis B viruses or exchanges of DNA sequences that determine HBsAg/ay and HBsAg/ad to form a new genotype.
The Release of a Platelet-Activating Factor by Stimulated Rabbit Neutrophils
Authors: Lynch James M. , Lotner Gary Z. , Betz Sally J. , Henson Peter M.
Published: December 2022

Normal rabbit peripheral blood neutrophils released a platelet-activating factor upon stimulation by opsonized zymosan. The liberation was Ca++ dependent and the time course of release was closely associated with phagocytosis. The material extracted into chloroform and exhibited an identical mobility by thin layer chromatography to basophil-derived, IgE-stimulated, platelet-activating factor (PAFb). It was similar to PAFb in its effect on platelets in both aggregation and release but was distinguished from ADP, thrombin, arachidonic acid, and thromboxanes. This factor appears to be responsible for some previously reported neutrophil-platelet interactions.
Qa-1-Associated Antigens
Authors: Kastner Daniel L. , Rich Robert R. , Chu Lily
Published: December 2022

The Qa-1b allele is assigned to strains whose peripheral lymphocytes are not lysed by a standard anti-Qa-1 serum. In order to investigate whether Qa-1b represents a single allele or several alleles that have been grouped together as “not a,” we studied the activity of cytotoxic T lymphocytes (CTL) specific for Qa-1b-associated antigens. Cold target inhibition experiments were performed to test the ability of various Qa-1b targets to inhibit the lysis of 51Cr-labeled B10 blasts by B10.BR anti-C3H and C57BR anti-AKR CTL. Qa-1a targets did not inhibit lysis relative to controls syngeneic with the CTL. In contrast, Qa-1b cold targets strongly inhibited the lysis of labeled B10 targets. We found no differences in inhibition among 16 Qa-1b strains representing six H-2 haplotypes and nine different backgrounds. These data indicate that all of these Qa-1b strains express the Qa-1 antigens shared by B10 and C3H or AKR, and thus suggest that Qa-1 is markedly less polymorphic than H-2.

Experiments were also performed to test the possibility that Qa-1-associated antigens are involved in the recognition of minor histocompatibility determinants. CTL were generated in secondary cultures between strains identical at Qa-1 and at H-2, but differing at minor histocompatibility loci. These CTL were tested for their ability to lyse targets bearing the minor histocompatibility antigens of the stimulators, and sharing either Qa region or H-2 antigens with the stimulators. In contrast with the well established role for H-2K and H-2D antigens in the recognition of conventional determinants, we found that in both Qa-1a and Qa-1b strain combinations, Qa region homology was neither necessary nor sufficient for minor locus-specific lysis.
Nature of T Lymphocyte Recognition of Macrophage-Associated Antigens
Authors: Thomas David W. , Meltz Susan K. , Wilner George D.
Published: December 2022

Strain 2, strain 13, or (2 × 13)F1 guinea pigs were immunized with human fibrinopeptide B, a 14 amino acid thrombin-derived fragment of the Bβ chain of fibrinogen (Bβ1-14), or the Bβ1-13 homologue, and in vitro T lymphocyte responsiveness was determined by the incorporation of 3H-thymidine. T cells from strain 2 or (2 × 13)F1 animals immunized with Bβ1-14 showed proliferative responses with Bβ1-14 but were unresponsive with Bβ1-13. Bβ1-13, Strain 13 Bβ1-14 immune T cells were unresponsive with both Bβ1-14 and 1–13. By contrast, T cells from strain 13 or (2 × 13)F1 guinea pigs immunized with Bβ1-13 produced proliferative responses with Bβ1-13 but not with Bβ1-14. Strain 2 Bβ1-13 immune T cells showed minimal or no responsiveness with Bβ1-13 or 1–14. Thus, responsiveness to Bβ1-14 is associated with strain 2 animals, and responsiveness to Bβ1-13 is associated with strain 13 guinea pigs. To determine the role of macrophages in presentation of Bβ1-14 or 1–13, T cells from (2 × 13)F1 guinea pigs immunized with Bβ1-14 or 1–13 were stimulated by antigen in association with macrophages derived from either parent. F1 T cells immunized with Bβ1-14 responded to Bβ1-14 in association with only strain 2 but not strain 13 macrophages. By contrast, Bβ1-13 immune F1 T cells responded with Bβ1-13 in association with only strain 13 but not strain 2 macrophages. These results are discussed with respect to the role of macrophages in selecting immunogenic determinants of peptide antigens for presentation to T cells.
Cells with Fc IgG Receptors in 69-Hr-Old Chicken Embryo
Authors: Nowak Jerzy S. , Lassila Olli , Granfors Kaisa , Toivanen Paavo
Published: December 2022

Receptors for the Fc fragment of IgG (Fc receptors) are expressed on a wide variety of normal cells including macrophages, polymorphonuclear leukocytes, B cells, some classes of T cells, mast cells, platelets, and different epithelial cells (1–5). They have also been described on various malignant cell populations including lymphomas, leukemias, plasma cell tumors, and various sorts of connective tissue and epithelial tumors (1). In addition, Fc receptors have also been detected on some virus-infected cells (6, 7).

During embryonic development, progenitors of mouse macrophages in the 10-day yolk sac have been found as the first cells possessing Fc receptors (8). It has also been suggested that bone marrow stem cells in the mouse are devoid of Fc receptors, although they are present on mature B lymphocytes (9). Owen et al. (10) have employed organ cultures to study the development of B lymphocytes in embryonic hematopoietic tissues of mouse.
Trans Gene Complementation of I-E Subregion Antigens
Authors: Silver Jack
Published: December 2022

The murine I-E subregion antigens consist of two polypeptide chains designated α and β with m.w. of 32,000 and 29,000, respectively. These murine antigenic complexes can be precipitated with specific alloantiserum from mice possessing an I-E subregion derived from H-2 haplotypes k, d, p, or r (1–5). Other mice either do not express the I-E subregion antigen or have it in a serologically undetectable form (5–7). Although the appropriate I-E subregion (I-Ed, p, k, or r) is necessary for detection of I-E subregion antigens, the structural polymorphism of Eβ chains is determined by a gene outside the I-E subregion and within the K to I-B genetic interval of the major histocompatibility complex (MHC) (8–10). This observation was made after studies by Jones et al. (5) indicated that expression of I-E subregion antigens required two genes, one in the I-A subregion and the other in the I-E subregion, and suggested that this might explain why for some mice maximum immune responses require complementation by two genes, one in the I-A or I-B and the other in the I-E or I-C subregion.
Characterization of a Spontaneous Murine B Cell Leukemia (BCL1)
Authors: Knapp M. R. , Jones P. P. , Black S. J. , Vitetta E. S. , Slavin S. , Strober S.
Published: December 2022

The surface marker expression of a spontaneous B lymphocyte leukemia discovered in a BALB/c mouse (BCL1) was examined and found to include a subset of markers known to occur on normal B lymphocytes. The tumor cells bore surface Ig that included both µ- and δ-chains associated with the λ light chain. Alloantigens coded for within the murine MHC, including H-2D, H-2K, and I-region products, were identified on the tumor cells. Although normal B lymphocytes are thought to express products coded for within both the I-A and I-E subregions, the BCL1 expressed only normal amounts of I-E subregion products. In addition, the H-2 and Ia antigens revealed by 2-dimensional gel electrophoresis exhibited an abnormal pattern of post-translational modifications. The Fc, but not the complement-receptor, was present on the surface of tumor cells. The presence of IgD, Ia antigens, and the responsiveness to lipopolysaccharide (see subsequent paper) have led us to postulate that the BCL1 tumor represents a later differentiative stage than murine B lymphocyte tumors previously described.
Heterogeneity of Binding of Human IgA Subclasses to Protein A
Authors: Brunda Michael J. , Minden Percy , Grey Howard M.
Published: December 2022

The ability of human IgA myeloma immunoglobulins to interact with protein A-containing Staphylococcus aureus was examined. Some IgA1 and IgA2 immunoglobulins bound to S. aureus although others of both subclasses failed to do so. These results were obtained by using both direct binding of radiolabeled immunoglobulins to S. aureus and with inhibition-type assays. Binding was dependent on the Fc fragment of IgA since there was no binding to S. aureus by an F(ab′)2 fragment of IgA1. Nonprotein A-containing bacteria did not bind these immunoglobulins and isolated protein A interacted with radiolabeled immunoglobulins. This strongly suggested that protein A was responsible for the observed binding to S. aureus. These data indicate, in contrast to previous reports, that there is no simple relationship between IgA subclass and the capacity to bind to protein A.
Biologic Activity of Rabbit Antisera Directed against in Vitro Stimulated Guinea Pig T Lymphocytes
Authors: Thomas David W. , Meltz Susan K. , Hahn Yaffa , Schwartz Benjamin D.
Published: December 2022

In this communication we examined the functional activity of rabbit antisera produced against guinea pig T lymphocytes that had been stimulated in vitro by culture with macrophage-associated antigen. One antiserum (96-2) was raised against strain 13 T cells that were primed by culture for a week with trinitrophenyl-(TNP) modified syngeneic macrophages. Addition of 96-2 serum to TNP-primed strain 13 T cells or strain 13 T cells primed in a mixed leukocyte reaction (MLR) stimulated a dramatic increase in DNA synthesis in vitro. In contrast, strain 13 T cells primed in vitro with several protein antigens failed to be stimulated by the 96-2 serum. In addition, 96-2 serum produced little stimulation of TNP or MLR-primed strain 2 cells, or of strain 13 T cells taken directly from the animal. Another antiserum (144-2) was raised against glutamic acid-lysine copolymer (GL)-immune strain 2 T cells selected by culture with GL-pulsed strain 2 macrophages. Addition of 144-2 serum to GL-selected or MLR-primed strain 2 T cells also produced a dramatic proliferative response. However, 144-2 serum did not stimulate TNP-primed strain 2 or strain 13 T cells, or strain 2 T cells selected with unrelated protein antigens. By several techniques we showed that contaminating B cells in the primed T cell preparations were not responsible for the observed proliferation and that the antisera directly stimulated highly purified T cells. The proliferative activity of 96-2 and 144-2 could be removed by absorption with nonimmune spleen cells. Physicochemical analysis of the cellular antigens detected by the antisera showed molecular species of 98,000, 70,000, 33,000 and 25,000 daltons. By sequential immunoprecipitation analyses, the latter two peaks were determined to be Ia antigens, the 70,000 peak of in vitro primed cells contained some immunoglobulin-like molecules and another nonimmunoglobulin-like antigenic species, and the 98,000 species appeared unrelated to immunoglobulin or Ia antigens.
Regulation of Contact Sensitivity to Dnfb in the Mouse: Effects of Adult Thymectomy and Thymic Factor
Authors: Erard D. , Charreire J. , Auffredou M. T. , Galanaud P. , Bach J. F.
Published: December 2022

The contact sensitivity response to DNFB is decreased after adult thymectomy (ATX). This response decreases to 50% of the control response of normal age-matched mice as soon as 3 weeks after ATX and is not further depressed 9 to 16 weeks after ATX. These results suggest that two T cell subsets of different lifespan are involved in the anti-DNFB response. A circulating thymic factor (FTS) is able to restore the contact sensitivity response to DNFB when injected 3 to 9 weeks after ATX but not 16 weeks later. By contrast, FTS has a depressive effect on the contact sensitivity response to DNFB of normal mice through a cyclophosphamide-sensitive T cell subset. These results suggest that FTS regulates DNFB contact sensitivity by acting on a cyclophosphamide-sensitive T cell subset, still present 9 weeks after ATX but absent after 16 weeks. Thus although the T cell defect, causing a depression of the contact sensitivity reaction to DNFB is quantitatively similar 3 and 16 weeks after ATX, its nature is probably different.
Studies of Reticuloendothelial Function in the Mouse with Model Immune Complexes
Authors: Finbloom David S. , Plotz Paul H.
Published: December 2022

We have extended the findings in the accompanying paper by characterizing the serum clearance and tissue uptake of model soluble immune complexes and the saturation of the reticuloendothelial system (RES) by these complexes in normal mice and in mice with murine lupus (NZB/W F1 females). Adult NZB/W or young C3H mice were injected with radiolabeled stable site-specifically cross-linked mouse anti-DNP oligomers as model immune complexes to proble RES function. Blood clearance and uptake by liver, spleen, and kidney were unimpaired in NZB/W mice. To determine if the RES exhibits partial saturation in the NZB/W mice, we deliberately induced a state of RES blockade with heat-aggregated human γ-glubulin (HAG). With increasing doses of HAG (1 to 4 mg/20 g body weight) both strains similarly showed a progressive increase in RES saturation as measured by reduced liver upake of model oligomers. Recovery from saturation was complete by 120 min in both strains. At maximal liver saturation there was only a small increase in oligomer uptake by kidney or spleen, the majority of complexes remaining within the circulation. Thus, RES capacity for handling soluble model immune complexes appears unimpaired in NZB/W mice.
Glucocorticoid-Induced Inhibition of T Cell Growth Factor Production
Authors: Gillis Steven , Crabtree Gerald R. , Smith Kendall A.
Published: December 2022

The previous communication presented data detailing that glucocorticoid hormones exhibited slight but significant inhibitory effects on the proliferation of cytolytic T cells maintained in long-term T cell growth factor (TCGF)-dependent cultures. However, most importantly, glucocorticoids were shown to inhibit T-lymphocyte proliferation via a profound effect on TCGF production. Addition of exogenous TCGF to glucocorticoid-treated human, mouse, or rat T cell mitogen-stimulated lymphocytes restored normal levels of proliferation. These observations led us to propose that the immunosuppressive effects of glucocorticoid hormones were mediated by controlling the production of the T cell proliferation-inducing agent, TCGF.

Results of experimentation detailed in this communication provide further evidence in support of this hypothesis. We found that although glucocorticoid hormones had little effect on the cytolytic reactivity of T cells harvested from TCGF-dependent culture, treatment of mixed lymphocyte cultures (MLC) with identical glucocorticoid hormone concentrations completely abrogated in situ TCGF production and alloantigen-directed cytolysis. The inhibitory effects of glucocorticoids in MLC could be eliminated once again simply by the delayed addition of exogenous TCGF. These observations coupled with those detailed in the previous report provide evidence that, rather than effecting lysis of potentially reactive mature lymphocytes, glucocorticoids influence the development of T cell-mediated immune reactivity by inhibiting TCGF production, which in turn serves to inhibit the clonal expansion of activated T cells.
Tissue Distribution of Immunoglobulin-Secreting Cells in Normal and IgA-Deficient Chickens
Authors: Clinton Lawrence E. , Arnaud-Battandier Franck , Koski Irma R. , Dooley Nancy J. , Muchmore Andrew V. , Michael Blaese R.
Published: December 2022

A reverse hemolytic plaque assay was employed to enumerate lymphoid cells actively secreting either immunoglobulin (Ig)G, IgA, or IgM in the small intestine, lungs, and lymphoid organs of normal and IgA-deficient chickens. In normal birds, intestinal lamina propria lymphocytes were proportionately richest in cells secreting IgG and IgA whereas the bone marrow was richest in IgM-secreting cells. The highest ratio of IgA to IgG secreting cells was also found in the lamina propria lymphocytes of the intestine (0.9), followed by the IgA to IgG ratios in the intestinal epithelium (0.31), and the lungs (0.19). The IgA to IgG ratios in the bone marrow (0.08) and the spleen (0.02) were considerably lower. Thus, both the intestine and the lungs were relatively enriched in cells actively secreting IgA. These IgA-secreting cells are the likely source of the IgA found in such quantities in intestinal and respiratory secretions.

The tissue distribution of Ig-secreting cells was also studied in two generations of birds with experimentally induced IgA deficiency. There was a striking diminution of IgA-secreting cells in all tissues, including the intestine and lungs, whereas cells secreting IgG and IgM were normal or increased. The lack of IgA-secreting cells in these birds represents the effects of donor suppressor T cells having specificity for IgA.
Human IgE Biosynthesis in Vitro: Studies with Atopic and Normal Blood Mononuclear Cells and Subpopulations
Authors: Fiser Paul Martin , Buckley Rebecca H.
Published: December 2022

IgE synthesis was investigated in cultures of unfractionated human blood mononuclear cells and of T- and B-enriched subpopulations. The facts that IgE released from initial cell pellets by a pH 3.7 buffer or freezing and thawing was much smaller in amount than in 7-day supernatants and that IgE production was markedly inhibited by puromycin and/or mitomycin C provided evidence for synthesis. The geometric means of PWM-stimulated and unstimulated IgE synthesis did not differ statistically. Unfractionated and B-enriched cells from 15 atopic donors with elevated serum IgE made significantly more IgE than did those from normals (p = <0.0001). Co-cultures of patient and control unstimulated and unfractionated cells produced less IgE than expected for 11 of 15 patients, with the overall geometric mean being 62% less (p = <0.05). B cells from some patients showed marked augmentation of IgE synthesis, suggesting that autologous T cells had had some suppressive effect. Assays of the same B cell supernatants for IgM failed to show similar augmentation. This observation and the finding of IgE production by unstimulated cells suggest that the IgE synthesis may have been stimulated in vivo. Recombinations of T and B cells revealed a greater tendency for T cells from normals to suppress IgE synthesis by patient B cells than did autologous T cells (p = NS). These data support the possibility that atopics have a relative deficiency of a regulatory cell or function that in normals prevents excessive IgE production. The fact that co-culturing patient T with normal B cells did not markedly increase IgE synthesis suggests that differences between normals and atopics involve both the T and the B subpopulations.
Measurement of Cell-Mediated Inflammation in Experimental Murine Autoimmune Encephalomyelitis by Radioisotopic Labeling
Authors: Scott Linthicum D. , Mackay Ian R. , Carnegie Patrick R.
Published: December 2022

A radioisotopic index test was used to detect that time of onset and intensity of cell-mediated immune inflammation of experimental autoimmune encephalomyelitis (EAE) in mice. Mice were tested at various time intervals after an encephalitogenic immunization with mouse spinal cord homogenate for delayed-type hypersensitivity (DTH) to myelin basic protein (MBP) by intradermal challenge with antigen in the ear pinna. After 24 hr, the intensity of DTH was measured by 125I-radiometry which depends upon the migration of 125I-UdR radiolabeled mononuclear cells into the antigen depot. Cells reactive to MBP were detected by the ear assay as early as 7 days after the initial encephalitogenic sensitization. The degree of cell-mediated immune inflammation in the brain and spinal cord during the evolution of EAE was also measured by a radioisotopic technique; increased 125I-UdR uptake could be detected in the brain 3 to 4 days before the onset of signs of EAE at days 11 to 12, whereas 125I-UdR in the spinal cord was detected only 1 day before, or concomitant with, the onset of signs of EAE. Both the “ear” and “organ” radiometric index tests are useful in measuring the degree of cell-mediated inflammation in EAE, and supplement routine histopathological and observational assessments.
Effector mechanisms of cytolytically activated macrophages. I. Secretion of neutral proteases and effect of protease inhibitors.
Authors: Adams D O
Published: December 2022

Peritoneal macrophages from C56BL/6J mice, when activated by bacillus Calmette-Guérin, lysed syngeneic MCA-I sarcoma targets but not syngeneic embryo fibroblasts. Inflammatory macrophages elicited by concanavalin A (Con A) did not appreciably lyse either target. The activated macrophages secreted more neutral proteases into the extracellular compartment, both absolutely and relative to intracellular content, than did the Con A inflammatory macrophages. Bovine pancreatic trypsin inhibitor (BPTI) (750 KIU/ml) and diisopropylfluorophosphate (2 x 10(-3) M) inhibited cytolysis of neoplastic targets by the activated macrophages. The BPTI had to be present during the 48-hr macrophage-tumor cell interaction to reduce cytolysis; pretreatment of either the macrophages or the targets by the BPTI did not reduce cytolysis. The inhibitors, at the concentrations found to inhibit cytolysis, were not toxic to the macrophages as judged by morphology, by the ability of the macrophages to incorporate leucine into protein, and by the potential for cytolytic activation of the macrophages in vitro. It is suggested that neutral serine protease(s) secreted by activated macrophages participate in the cytolytic destruction of neoplastic cells.
Complement receptors on guinea pig epidermal Langerhans cells.
Authors: Berman B , Gigli I
Published: December 2022

A population of guinea pig epidermal cells possessed the ability to form rosettes with IgM antibody-sensitized sheep erythrocytes coated with purified human C3b (SEAIgMC1-), but not with intermediates carrying C1, C4, or C2. This population of rosette-forming epidermal cells was identified as Langerhans cells (LC) ultrastructurally and by LC depletion and enrichment studies. In addition, these cells were able to bind fluid phase C3b, which inhibited any subsequent SEAIgMC1-3b rosette formation. Rosette formation was also inhibited after SEAIgMC1-3b pretreatment with beta 1H and C3b-inactivator. LC were shown to possess trypsin-resistant C3b and Fc receptors, and unlike the temperature-independent nature of LC Fc-rosette formation, the ability of LC to form C3 rosettes was a temperature-dependent process. The finding of C3b receptors on the surface of guinea pig epidermal LC supports the concept that they are of the phagocytic monocyte-macrophage family.
The effects of dialyzable products from human leukocyte extracts on cutaneous delayed-hypersensitivity response.
Authors: Gottlieb A A , Maziarz G A , Tamaki N , Sutcliffe S B
Published: December 2022

Fractions from human whole leukocyte lysates were prepared by sequential double dialysis against membranes with cut-offs of m.w. 12,000 and 3500, and by elution chromatography on Sephadex G-10. The effect of localized intracutaneous implantation of fractions with m.w. less than 3500 was studied. Two types of response were obtained: 1) the amplification of response to antigen to which the donor had preexisting immunity, and 2) the induction of inflammatory response histologically resembling delayed hypersensitivity in the absence of added antigen. The substances mediating these responses could be separated into unique components by use of a long (1 x 150 cm) G-10 column, or by hydroxylapatite chromatography. The active principles were derived from leukocyte extracts (as demonstrated by their absence from autologous RBC extracts prepared by identical methodology), and the histopathologic appearances after intracutaneous implantation were compatible with those of a delayed-hypersensitivity response. No evidence of transfer of antigen-specific information from a sensitive donor to a nonsensitive recipient was obtained under the conditions of study.
Mitogenic effect on human lymphocytes of insolubilized anti-immunoglobulins. I. Specificity of the stimulating agent.
Authors: Henriksen A , Godal T , Landaas T O
Published: December 2022

The mitogenic response of peripheral blood lymphocytes to various anti-immunoglobulin reagents has been studied by measuring incorporation of a radioactive thymidine into macromolecules. Coupling of anti-F(ab')2 or anti-light chain antibodies to Sepharose beads leads to a 5-fold increase in their mitogenic capacity with 50-fold less antibodies per culture. Pepsin-digested F(ab')2 fragments had a mitogenic capacity similar to intact antibody molecules. Anti-F(ab')2 antibodies purified by immunoabsorbent columns were found to be more effective as mitogen than unpurified antibody fractions. Antibodies to kappa- or lambda-light chains were found to be mitogenic, whereas antibodies specific to various heavy chain classes failed to induce a significant response. Isolated light chains were much more effective in inhibiting the reaction than isolated mu-chains. It is concluded that insolubilized anti-light chain antibodies are mitogenic to human peripheral blood lymphocytes.
Control of autologous immune complex nephritis. I. Suppression of the disease in the presence of T cell sensitization.
Authors: Harmon W E , Grupe W E , Parkman R
Published: December 2022

Pretreatment of Lewis and Sprague-Dawley rats with the nephritogenic antigen, Fx1A, in incomplete Freund's adjuvant (IFA) reduced the incidence of autologous immune complex nephritis in rats subsequently challenged with Fx1A in complete Freund's adjuvant (CFA). The suppression was evidenced by a decrease in antibody production, in glomerular deposition of immunoglobulins, and in the incidence of proteinuria, and it was antigen specific. In vitro blastogenesis to Fx1A of lymphocytes from Fx1A-IFA-pretreated animals was normal. Rats pretreated with Fx1A-IFA initially developed a normal antibody response after challenge with Fx1A-CFA, but the response was not sustained. These results indicate that the Fx1A-IFA-induced suppressor mechanism does not inhibit sensitization, but rather modifies specific antibody production.
Serum antibodies to human fetal antigens in patients with systemic lupus erythematosus (SLE).
Authors: Linker-Israeli M , Quismorio F P , Wong D K , Friou G J
Published: December 2022

Serum antibodies to human fetal antigens were measured by a radiolabeled anti-immunoglobulin binding assay by using human fetal fibroblasts (Flow cell line No. 1000) as target cells. High titers of IgG antibody to the fetal cells were found in sera of patients with systemic lupus erythematosus (SLE). The antibody reacted with surface membrane antigens shared by various fetal tissues of human and murine origin but not by adult tissues. The reaction of the SLE antibody to the fetal cells was inhibited by heterologous antiserum to the Flow 1000 cells and antiserum to murine embryonic fibroblasts, but not by antiserum to human alpha-fetoprotein or human fibronectin. Absorption of SLE serum with isolated nuclei did not abolish the reaction indicating that these were not anti-nuclear antibodies. The antibody activity was found to reside in the F(ab')2 fragment. The serum titer of the anti-fetal antibody was higher in SLE patients with active disease than those in clinical remission.
Reduced natural killer activity in female mice after neonatal exposure to diethylstilbestrol.
Authors: Kalland T
Published: December 2022

Treatment of neonatal female mice with DES markedly reduced the activity of NK cells in adult mice. This finding was most evident in C57BL/6 and BALB/c strains, but was also found in outbred NMRI mice. The mechanisms behind the reduced NK activity was further analyzed. No evidence of DES-induced cellular or humoral suppressors of natural killing could be detected. Pregnancy was found to be without effects on NK. Poly I:C augmented the NK activity in control females but even very high doses of Poly I:C failed to increase the level of NK activity in neonatally DES-treated animals. The lack of response to boosting with Poly I:C was not due to alterations in kinetics of NK induction.
Monohydroxyeicosatetraenoic acids (HETEs) induce degranulation of human neutrophils.
Authors: Stenson W F , Parker C W
Published: December 2022

5-S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), a lipoxygenase product in neurophils, and 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), a lipoxygenase product in platelets, were prepared biosynthetically and incubated with purified human peripheral neutrophils. Both 5-HETE and 12-HETE at 5- to 10-microM concentrations induced degranulation of specific granules. Both 5-HETE and 12-HETE are chemotactic for neutrophils at these concentrations. Arachidonic acid, the metabolic precursor of 5-HETE and 12-HETE, did not induce degranulation. The calcium ionophore A23187 induces neutrophils degranulation and also activates arachidonic acid metabolism in neutrophils resulting in 5-HETE production. Both ionophore-induced 5-HETE production and ionophore-induced degranulation can be inhibited, with very similar inhibition curves, by 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonate metabolism. We propose that the mechanism for 5-HETE- and 12-HETE-induced degranulation is an alteration in the fatty acid composition of membrane phospholipids.
Qualitative and quantitative changes in the antibody producing cell response to lipopolysaccharide induced after incorporation of the antigen into bacterial membrane phospholipid vesicles.
Authors: Ruttkowski E , Nixdorff K
Published: December 2022

Lipopolysaccharide (LPS) isolated from Proteus mirabilis and administered to mice i.p. induced a primary immune response that consisted of the proliferation of only IgM antibody-producing cells. The response to a second stimulus 14 days later was also predominantly IgM, although a smaller number of IgG-producing cells was detected. The strength of the responses depended upon the dosage of LPS administered. When mice received a primary injection of the same amount of LPS incorporated into P. mirabilis phospholipid vesicles, the number of IgM-producing cells was significantly increased over that induced by LPS alone. In addition, IgG-producing cells appeared on day 5 and increased during the time course measured up to day 14. After a booster injection of the same amount of LPS-phospholipid vesicles on day 14, the numbers of IgM-producing cells increased approximately 3-fold and the numbers of IgG-producing cells approximately 16-fold over those of mice given LPS alone. These results demonstrate a pronounced adjuvant effect of bacterial membrane phospholipids that are able to alter not only the strength but also the type of response to LPS.
In vitro induction of IgM secretion and switching to IgG production in human B leukemic cells with the help of T cells.
Authors: Saiki O , Kishimoto T , Kuritani T , Muraguchi A , Yamamura Y
Published: December 2022

In vitro stimulation of the B leukemic cells (B-CLL cells) with normal allogeneic T cells plus PWM induced IgM secretion and a switching from IgM to IgG production. Induction of IgM and IgG production in B-CLL cells with T cells was demonstrated by the presence of the same idiotype in induced Ig as that present in the monoclonal IgM protein in the patient's serum. Both T cells and PWM were required for Ig induction in B-CLL cells, and x-irradiated T cells showed the comparable helper effect. T cells and PWM induced not only Ig secretion but proliferation of B-CLL cells. Cell division was essential for the differentiation of the leukemic cells to Ig-producing cells. PWM-induced, antigen-nonspecific helper factor(s) were also effective in the induction of differentiation of the leukemic cells. Variations existed among T cell donors in the capabilities to induce differentiation of the same leukemic cells, suggesting the requirement of matching of acceptors on B-CLL cells and T effector molecules for the induction of Ig production in B-CLL cells.