bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Human B Lymphocytes
Authors: Haynes Barton F. , Fauci Anthony S.
Published: December 2022

The present study defines and characterizes multiple subpopulations of immunoregulatory human peripheral blood (PB) mononuclear cells of in vitro immunoglobulin (Ig) synthesis. The in vitro pokeweed mitogen-induced (PWM) anti-sheep red blood cell (anti-SRBC) plaque-forming cell (PFC) response and intracytoplasmic (ICP) Ig formation varied among normal subjects studied. On the basis of PFC responses, normal individuals can be divided into responders (>75 PFC/106 mononuclear cells) and nonresponders (<25 PFC/106 mononuclear cells). Furthermore, PB lymphocytes from PFC nonresponders also had decreased responses with regard to PWM-induced ICP Ig.

Irradiated and nonirradiated unfractionated (total) T cells from responders both provided a net helper effect for PFC induction and ICP Ig production when co-cultured with allogeneic B cell-enriched suspensions. Within the total T cell population from responder individuals, T cells with an Fc receptor (R) for IgG (TG cells) suppressed PFC responses, whereas corresponding TG-depleted T cells obtained after overnight incubation did not suppress PFC responses. In addition, the total non-T cell fraction from responders suppressed B cell function in allogeneic and autologous co-cultures. However, this responder non-T cell-mediated suppression of Ig synthesis was radioresistant and was abrogated by removal of adherent cells.

In contrast, nonirradiated total T cells from nonresponders did suppress PFC induction and ICP Ig production by allogeneic B cell-enriched suspensions. However, similar to responder individuals, irradiated total T cells from nonresponders not only did not suppress, but provided maximal T cell helper effect for PFC induction and ICP Ig production by allogeneic B cells. Furthermore, similar to responders, total non-T cell (E-rosette negative) fractions from nonresponders suppressed PFC responses in allogeneic co-cultures. However, this suppression was not abrogated by removal of adherent cells. The nonadherent suppressor cells in the E-rosette positive and E-rosette negative fraction from nonresponders bore an FcR for IgG. The primary difference between immunoregulatory cells found in responder and nonresponder subjects was the presence in nonresponders of E-rosette positive and E-rosette negative IgG FcR+ suppressor lymphocytes that did not require exposure to 7SEA to suppress.

Thus, the functional capabilities of immunoregulatory cell populations differ greatly among normal individuals and relate primarily to immunoregulatory control of Ig synthesis at the T cell level. These studies illustrate the complexities of human immunoregulatory cell functions as expressed in in vitro cultures and illustrate that many of the in vitro immunoregulatory abnormalities associated with disease states can be demonstrated under certain conditions in mononuclear cell suspensions from normal subjects.
Immunity to the T1699 Murine Mammary Tumor
Authors: Parthenais Elaine , Haskill Stephen
Published: December 2022

The effects of T cell depletion on anti-tumor effector mechanisms were investigated in ATXBM DBA/2 mice. In the absence of T cell immunity, the intra-tumor infiltrate was reduced as well as modified, the inflammatory response being more typical of an immediate than of a delayed hypersensitivity reaction. Monocytic “armed” and small ADCC effector cells were found inside the tumors of ATXBM mice but large phagocytic ADCC effector cells were absent. Accelerated tumor growth and reduced survival time were observed in the ATXBM hosts and 79% of these animals had overt signs of tumor growth at secondary metastatic sites. Invasion from the primary subcutaneous site through the peritoneal wall and seeding of the peritoneal cavity were also seen in these mice. On the other hand, CXBM tumor bearers were free of macroscopic metastases and had normal levels of in situ inflammatory cells. Lethal irradiation and bone marrow repopulation per se had little or no effect on tumor growth rate and survival time of the tumor bearers. The role of thymus-independent immediate hypersensitivity to the T1699 and of thymus-dependent delayed hypersensitivity and ADCC antibody on the intra-tumor localization of inflammatory cells and the control of tumor growth at primary and secondary sites are discussed.
Inhibition of Influenza-Immune T Cell Effector Function by Virus-Specific Hybridoma Antibody
Authors: Effros Rita B. , Frankel Mark E. , Gerhard Walter , Doherty Peter C.
Published: December 2022

The in vitro activity of influenza-specific cytotoxic T cells can be inhibited by incubation of the target cells with monoclonal anti-influenza antibodies. Hybridoma antibodies that bind to the virus HA inhibit the cytotoxic activity of TDL for the virus-infected target by as much as 80%, whereas these same antibodies never reduce splenic T cell function by more than 40%. This reflects the fact that TDL from anti-influenza strain A/WSN/33 (HON1) are highly subtype-specific, whereas splenic effector cells from the same mice are cross-reactive for target cells infected with heterologous influenza A viruses. These findings are discussed in the light of previous failures to block virus-immune T cell effector function with heterogeneous antisera produced in vivo, and are considered to favor the idea that at least some of the “virus-immune” T cells are indeed recognizing viral antigens.
Passive Enhancement of Mouse Tumor Allografts by Alloantibodies Is Fc-Dependent
Authors: de Waal Robert M. W. , Cornelissen Ine M. H. A. , Capel Peter J. A. , Koene Robert A. P.
Published: December 2022

Enhancement of growth of a B10.D2 fibrosarcoma in B6AF1 recipients could be induced by administration of B6AF1 anti-B10.D2 lymphocyte serum. The role of the Fc part in this phenomenon was studied by treatment of the B6AF1 recipients with F(ab′)2 fragments of enhancing alloantibodies. A highly purified F(ab′)2 preparation was used to exclude any effects of undigested IgG. Administration of F(ab′)2 did not lead to enhancement of the tumor allografts, not even when given in a dose that was 22 times the molar amount of the lowest enhancing dose of undigested IgG. We therefore conclude that passive enhancement of mouse tumor allografts by alloantibodies is Fc dependent.
In Vitro Antibody Response to Influenza Virus
Authors: Anders E. Margot , Peppard Prudence M. , Burns William H. , White David O.
Published: December 2022

A good secondary IgG response to the hemagglutinin (HA) of influenza virus has been obtained in vitro in Marbrook-type cultures of influenza-primed mouse spleen cell suspensions stimulated with inactivated influenza virus. Anti-HA antibody was quantitated by a solid phase radioimmunoassay (RIA) by using purified HA as substrate. The T dependence of this secondary response was shown by depletion of T cells and reconstitution with a source of primed or unprimed T cells. The help given by T cells primed to the homologous virus was many times greater than that given by unprimed T cells. Although the latter was significant. The system described will allow investigation of the specificity requirements of helper T cells engaged in the anti-HA response.
Evidence for an Ester Linkage between the Labile Binding Site of C3b and Receptive Surfaces
Authors: Law S. K. , Lichtenberg N. A. , Levine R. P.
Published: December 2022

The labile binding site of C3b interacts with receptive surfaces by way of a covalent bond. We report here experiments directed toward elucidating the nature of the linkage. 125I-C3b was bound to zymosan (Z) carrying C3-convertase activity on its surface. The resulting zymosan-C3b particles (Z-C3b) were washed free of noncovalently bound proteins with 1% SDS. The Z-C3b particles were incubated at different pH's, and it was found that C3b can be released under alkaline conditions but not acidic conditions. Release of C3b can also be observed at alkaline pH in the presence of 1 M hydroxylamine. The kinetics of the release of C3b from Z were studied at pH 7.5 in 1 M hydroxylamine and at pH 10 in 0.1 M NaHCO3. The second order rate constants for the release of C3b from Z were found to be 0.0026 ± 0.003 M-1 min-1 in hydroxylamine at neutral pH, and 37 ± 3 M-1 min-1 at pH 10. These values are comparable to the rate constants for the hydroxylaminolysis and hydrolysis of compounds containing esters such as benzoyl glycine ethyl ester, acetylcholine, and N,O-diacetylserinamide. They are significantly different, however, from the values obtained for the hydroxylaminolysis and hydrolysis of compounds containing thioesters, tyrosyl esters, and acylimidazole. The results of these experiments are consistent with the hypothesis that the bond between C3b and receptive surfaces is an ester. Further evidence for an ester linkage between C3b and receptive surfaces was obtained by analyzing the products of the release of C3d from zymosan by hydroxylamine. If the bond is indeed an ester, the release of C3d from Z with hydroxylamine will yield an hydroxamate that either associates with C3d or with Z. We were able to detect 0.66 ± 0.12 moles of hydroxamate per mole of C3d peptide, suggesting that the bond between C3b and receptive surfaces (RS) takes the form of RS-O-CO-C3b.
Modulation of Granulomantous Hypersensitivity
Authors: Chensue Stephen W. , Boros Dov L.
Published: December 2022

The cellular basis of the spontaneous modulation of the granulomatous response to schistosome eggs was analyzed in mice infected with Schistosoma mansoni. Spleen cells of 20 or 32 week-infected mice undergoing modulation, when transferred to 6 week-infected recipients, suppressed the maximal granulomatous response at 8 weeks. Suppression of both naturally forming asynchronous liver and synchronously induced lung lesions was achieved. Specificity of this effect was demonstrated by the suppression of egg granulomas but not antigen-coated bead granulomas developing simultaneously in the lungs of cell recipients. Further characterization showed that suppression was abrogated by pretreating transferred cells with either anti-Thy 1.2 or anti-Iak alloantisera and C. Transfer of macrophage-depleted or fractionated T and B spleen cells confirmed that T cells alone transferred suppression. Moreover, an Ia antigen-bearing (Ia+) subpopulation of T cells was required in the transferred population. An examination of T cells obtained from isolated, dispersed lung granulomas from control and adoptively suppressed mice revealed an increased proportion of Ia+ cells in the latter. It is suggested that Ia+ T cells may be involved in the local modulation of the granulomatous response.
Identification of Two HBeAg Subspecificities Revealed by Chemical Treatment and Enzymatic Digestion of Liver-Derived HBcAg
Authors: Budkowska Agata , Kalinowska Bozenna , Nowosławski Adam
Published: December 2022

The complete hepatitis B virus (HBV)2 is now believed to be the 43-nm Dane particle composed of a 27-nm core (HBcAg) and an antigenically different coat (HBsAg). The core particle represents the nucleocapsid of HBV and contains a double stranded circular DNA molecule and DNA polymerase. HBeAg is considered to be the third HBV-specified antigen representing a complex of soluble proteins having a common reactivity toward sera containing anti-HBe in immunodiffusion tests. The diversity of the HBeAg system has been well documented by immunodiffusion: there appear to be at least three different reactivities: HBeAg/1, HBeAg/2, and HBeAg/3.

A number of studies have demonstrated that the presence of HBeAg correlates well with that of Dane particles in serum and of HBeAg in liver cell nuclei. These correlations have recently been explained by demonstrating the presence of HBeAg in a cryptic form in core particles from serum (1) and liver (2).
Alloantigen-Activated CML Suppression Independent of Cytotoxic Activity
Authors: Orosz Charles G. , Bach Fritz H.
Published: December 2022

The generation of T cell-mediated lympholysis (CML) in murine mixed lymphocyte cultures (MLC) can be impeded if allogeneic responding and stimulating cells are incubated in the presence of lymphocytes that have been activated by prior exposure to alloantigens (1–6). The mechanism by which alloantigen-activated cells reduce levels of cytotoxic activity generated in fresh MLC remains to be determined. Several independent investigators have suggested that CML-suppressive cells are actually alloantigen-activated cytotoxic T cells (2, 4). These cells would diminish normal CML responses by eliminating MLC stimulator cells and, thus, the cell-borne signals required for CML generation. Other investigators, attempting to rule out this possibility, have relied on indirect arguments to support their contention (3, 6, 7). We herein report the generation and detection of potent CML suppressive activity under conditions in which cytotoxicity has been eliminated as a possible mechanism of suppression.

Materials and Methods. Mice.
Antibody-Mediated Immunosuppression of a Cytotoxic Cell Response Not Involving a Simple Antigen-Masking Mechanism
Authors: Sinclair N. R. StC. , Law F. Y.
Published: December 2022

An in vitro cytotoxic cell response against alloantigens was inhibited by antibody directed against the alloantigens and also by anti-trinitrophenyl antibody provided that the allogeneic stimulator cells were modified with trinitrophenyl. Inhibition of an anti-allogeneic cytotoxic cell response against trinitrophenyl-coupled allogeneic stimulator cells by anti-trinitrophenyl antibody is dependent upon the intact Fc portion of inhibitory antibody. The magnitude of the difference between intact and F(ab′)2 anti-trinitrophenyl antibody in immunosuppressive activity suggests that the Fc portion emits negative signals rather than simply adding to a steric hindrance effect.
Adenosine Receptor on Human Basophils: Modulation of Histamine Release
Authors: Marone Gianni , Findlay Steven R. , Lichtenstein Lawrence M.
Published: December 2022

Adenosine, at physiologic concentrations, inhibits in vitro IgE-mediated human basophil histamine release in a dose-dependent fashion. The inhibition dose-response curve is paralleled by an adenosine-induced increase in cAMP levels of human leukocyte preparations. Further evidence that the adenosine effect is related to changes in cAMP levels is that the nucleoside inhibits only in the first stage of antigen-induced histamine release and fails to inhibit the release caused by ionophore A23187. A poorly metabolized derivative of adenosine, 2-chloro-adenosine inhibits as effectively as adenosine; dipyridamole, which blocks adenosine uptake, does not impair the inhibition caused by adenosine. Finally, theophylline, which is a competitive antagonist of adenosine in human lymphocytes also blocks the inhibition of release caused by adenosine. These data suggest that adenosine acts via a specific cell-surface receptor linked to adenylate cyclase. It appears that the human basophil has a specific receptor for adenosine and that this nucleoside may modulate the in vivo release of the mediators of immediate hypersensitivity reactions.
Human Blood T Lymphocytes That Suppress the Mixed Leukocyte Culture Reactivity of Lymphocytes from HLA-B14 Bearing Individuals
Authors: Bean Michael A. , Akiyama Mitoshi , Kodera Yoshihisa , Dupont Bo , Hansen John A.
Published: December 2022

A nontransfused male patient with recurrent bladder carcinomata has been demonstrated to have blood T lymphocytes that suppress the MLC responsiveness of lymphocytes only from normal individuals positive for HLA-B14. Unexpectedly, this T-suppressor cell differs from three other reported blood T-suppressor cells arising in man in that it apparently does not require HLA-D locus compatibility between the suppressor cell and the lymphocyte being suppressed.
Delayed Advent of Stringent, Non-H-2 Genetic Regulation of the Antibody Response to a Protein Antigen
Authors: Kipp Dale E. , Furman Abraham , Miller Alexander , Sercarz Eli E.
Published: December 2022

The role of non-H-2 gene(s) in the control of the antibody response to three lysozymes was investigated. Upon secondary challenge, A/J (H-2a) mice generated at least a 25-fold greater anti-lysozyme plaque-forming cell response than did B10.A (H-2a) mice. Nearly equal, strong peak primary responses, predominantly IgG in nature, were obtained from both A/J and B10.A mice after a single challenge with lysozyme in complete Freund's adjuvant. However, clear differences in responses are seen within 5 days after the peak primary plaque-forming response and by day 28 at the serum antibody level. B10.A mice never equal their primary responses, whereas A/J mice demonstrate positive immune memory. It appears that a non-H-2 gene(s) that regulates the overall antibody level to a protein antigen becomes manifest only after an initial antibody response.
A New Clonogenic Technique for Human Mitogen-Responsive T Cells
Authors: Mercola Karen , Cline Martin J.
Published: December 2022

The present investigations were prompted by limitations of previously described assay systems for growing colonies of human T lymphocytes in soft agar. These limitations include low cloning efficiencies of 1 to 20 colonies generated per 1000 lymphocytes cultured, failure of colony formation at low cell concentrations (below 1 × 105 cells/ml), and requirements in some systems for prior incubation with phytohemagglutinin (PHA). This report describes an efficient clonogenic assay for mitogen-responsive human peripheral blood mononuclear cells under conditions that minimize the potential for agglutination and direct cell-cell interaction. Peripheral blood mononuclear cells were plated directly into agarcontaining PHA and autologous erythrocytes and after incubation were fixed and stained in situ. The plating efficiency was 10.3 ± 9.7 (S.D.) colonies/100 peripheral blood mononuclear leukocytes and between 10 and 64 colonies/100 mononuclear leukocytes depleted of B cells and monocytes and enriched in T cells. Optimal growth required the presence of autologous erythrocytes. Colony formation was ablated by anti-T cell serum and was resistant to cytotoxic anti-B cell serum; i.e., colonies were not B cells or CFU-C. The clonal nature of colonies generated was indicated by a linear dose-dependent relationship between colonies generated and the dilute cell cultures plated, in the range of 4 × 102 to 5 × 103 cells/ml, by geographical isolation of colonies, and by lack of colony formation with irradiated cells. This method has also been used successfully to clone an established human T cell line.
Role of L-Alanine in the Response of Human Lymphocytes to PHA and Con A
Authors: Rotter Varda , Yakir Yeshayahu , Trainin Nathan
Published: December 2022

The response of umbilical cord blood lymphocytes (UCBL) to PHA and Con A is strongly dependent upon the presence of dialyzable plasma components. The impaired response of human cells in the presence of dialyzed human plasma was restored by calf thymus extract. In the present experiments we have further purified calf thymus extract by means of paper electrophoresis and chromatography on thin-layer cellulose plates. We reached the conclusion that the active material in this model is a single amino acid, alanine. When the different isomeric forms of alanine were tested, we found that L-alanine is the only biologically active material. In addition, we have observed here that the allogeneic response of UCBL is also dependent upon the presence of dialyzable plasma components. This impaired allogeneic response of UCBL in the presence of DHP was restored by addition of L-alanine. The present findings suggest that, under in vitro conditions, for human cells to respond to mitogenic or allogeneic stimulation L-alanine is essential.
Genetic Control of Sensitivity to Moloney Leukemia Virus in Mice
Authors: Debre Patrice , Gisselbrecht Sylvie , Pozo Françoise , Levy Jean Paul
Published: December 2022

The level of viremia and the appearance of leukemias were studied after inoculation with Moloney leukemia virus (M-MuLV) in different H-2 congenic strains of mice. The viremia was regularly measured on individual mice with a radioimmunoassay of the major internal virion component p30. Three genes within the major histocom-patibility complex controlled the level of circulating virus. Two of them, called Rmv.1 and Rmv.2, appear to be located in the I region, respectively, in the IA, and the IC-S or G regions. The third gene, Rmv.3, was mapped to the D end of the complex in the D or T region. Crosses between resistant and sensitive strains demonstrated that the H-2 associated resistance was inherited as a dominant or semi-dominant Mendelian trait. Rmv.1, Rmv.2, and Rmv.3 were shown to complement for resistance in trans when the hybrids between sensitive strains were examined. A good correlation was found between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. Nevertheless, additional non-H-2 genes must control viremia and/or the appearance of leukemia since, despite high levels of viremia, some sensitive strains do not become leukemic.
Lepromin-Induced Suppressor Cells in Patients with Leprosy
Authors: Mehra Vijay , Mason Llewellyn H. , Fields James P. , Bloom Barry R.
Published: December 2022

The possibility of an active mechanism of immunologic suppression in leprosy was explored by assessing the in vitro lymphocyte responses of 61 leprosy patients and 30 normal individuals to the mitogen Con A in the presence or absence of Dharmendra lepromin. Lepromin-induced suppression of Con A stimulation was found in 32 of 35 lepromatous patients and 15 of 15 borderline patients, but only 2 of 15 tuberculoid patients and 2 of 30 normal controls. Cell fractionation studies indicated at least two cell populations involved in the in vitro lepromin-induced suppressor activity, adherent cells and Tγ-cells.
Target Cell Heterogeneity in Murine Leukemia Virus Infection
Authors: Isaak Dale D. , Price Joseph A. , Reinisch Carol L. , Cerny Jan
Published: December 2022

The susceptibility of mouse lymphocytes from various organs to infection by murine leukemia virus (MuLV) (Friend) was studied both in vivo and in vitro by using either Friend virus complex (FV) or lymphatic leukemic virus (LLV), the helper virus isolated from FV. Productively infected cells releasing infectious MuLV were identified as infectious centers (IC) on sarcoma+, leukemia- indicator fibroblasts. IC were detected by days 4 to 6 postinfection in spleen and bone marrow (BM); fewer IC were observed in lymph nodes (LN) and their appearance was delayed until day 8 in FV-infected mice and day 15 in LLV-infected mice. In both groups, the appearance of IC in LN correlated with the onset of splenomegaly (mean = 300 mg) and the development of infection in peripheral blood exceeding 1 × 106 focus-forming units/ml, suggesting that the IC observed in LN were due to dislodged, circulating infected spleen and BM cells rather than due to infection of LN cells. This possibility was tested directly by using a culture system whereby cells from spleen, BM, and LN from normal mice were infected with FV or LLV in vitro. The principal target for MuLV replication in the cultures appeared to be B lymphocytes because 1) stimulation with bacterial lipopolysaccharide (LPS) greatly enhanced the infection of unseparated BALB/c spleen and bone marrow cells, nylon wool-adherent BALB/c spleen cells, and spleen and BM cells from athymic (nude) mice, 2) pretreatment of spleen cells with a heterologous anti-mouse immunoglobulin antiserum plus complement reduced the infection, and 3) the majority of virus-permissive cells in BALB/c spleens were recovered in the pure population of Ig+ cells from an immunoadsorbent column. However, no IC were detectable in LPS-stimulated LN cells from either BALB/c or nude mice, confirming the fundamental difference in susceptibility to the MuLV component of FV between B cells from spleen, BM, and LN suggested by the in vivo studies.
Natural Killer Cells in Mice Treated with 89Strontium: Normal Target-Binding Cell Numbers but Inability to Kill Even after Interferon Administration
Authors: Kumar Vinay , Ben-Ezra Jonathan , Bennett Michael , Sonnenfeld Gerald
Published: December 2022

Natural Killer (NK) cell activity against YAC-1 lymphoma cells is greatly reduced in spleens of mice injected previously with the bone-seeking isotope, 89Sr. Spleen cells from 89Sr-treated mice filtered over nylon wool and Sephadex G-10 columns failed to increase the low NK cell activity. Cell mixture experiments failed to show inhibition of NK activity of normal spleen cells by spleen cells from 89Sr-treated mice. 89Sr produced lowering of NK activity in athymic nude mice similar to that seen in control mice. These experiments suggest that the low NK activity in 89Sr-treated mice is not due to the presence of thymus-dependent or independent suppressor cells active at the effector phase of NK cell-mediated killing. The low NK activity of 89Sr-treated mice could not be stimulated by administration of interferon inducers, polyinosinic:polycytidylic acid and Corynebacterium parvum, or by preparations containing type I or II interferons. The frequency of cells capable of binding to YAC-1 target cells in normal in spleens of 89Sr-treated mice. These data suggest that in 89Sr-treated mice, NK cells exist in a state in which they can bind the target cells but cannot lyse them and are unresponsive to the activating effect of interferons. Transformation of these cells into fully lytic and interferon-responsive cells appears to require an intact bone marrow. Bone marrow cell infusions failed to restore NK activity in irradiated or unirradiated 89Sr-treated mice, but were able to do so in normal lethally irradiated mice. Thus functional NK cells reactive against YAC-1 lymphoma cells are not only marrow derived but also marrow dependent.
Nonallelic Inheritance of VH Region a Group Allotypes: Cell Surface and Serum Studies in Double and Triple Expressing Rabbits
Authors: Wolf Benjamin , Urban Richard , Miller Ann B. , Kimball Edward S. , Mudgett Meredith , Catty David , Daneman Joanna
Published: December 2022

VH region latent allotypes have been detected in high concentration in the serum of a number of our rabbits in several litters. In some of these rabbits, the same allotypes were also found on the cell surface of peripheral blood lymphocytes (PBL) after proteolytic enzyme treatment and allotype regeneration in cell culture. However, although serum from several rabbits in these litters did not contain latent allotypes, nonallelic allotype was synthesized by a large percentage of PBL. Several types of nonMendelian inheritance patters were detectable: 1) Cyclic serum expression of serum a1 allotype was transmitted among members of three pedigreed litters although a2 and a3 were continuously displayed. This is the first report that bursts of synthesis of immunoglobulin markers may be under the control of transmitted genes. 2) A buck, an a1, a2, a3 (triple) expressor in the serum as well as on the cell surface, segregated nonallelic genes coding for a1 or a2 cell surface allotypes. In one sibling, both of these markers were inherited from the buck on the cell membrane, but not in the serum. 3) In another litter, derived from an a2,2 buck mated to an a1,3 doe, one rabbit showed periodic expression of a1 in the serum, but continuous expression of a2 and a3. The rabbit exhibited a1, a2, and a3 at the cell surface continuously. It is possible that several mechanisms are contributing to latent allotype inheritance in these rabbit families.
Polyclonal B lymphocyte activation during Trypanosoma cruzi infection.
Authors: Ortiz-Ortiz L , Parks D E , Rodriguez M , Weigle W O
Published: December 2022

Infection of A/J mice with Trypanosoma cruzi results in the polyclonal activation of B lymphocytes in vivo as assessed by the spontaneous plaque-forming cell (PFC) response to trinitrophenyl and to goat, equine, and sheep erythrocytes. The peak response to these antigens is found at 5 to 6 days of infection. Additionally, a polyclonal response to syngeneic erythrocytes can be detected in infected mice by using aged but not fresh indicator cells. Polyclonally stimulated PFC to human gamma-PFC found late in infection during a period of marked splenomegaly and parasitemia. This trypanosoma-induced polyclonal B cell activation may well be responsible for the abnormalities in immunoglobulin synthesis and secretion that have been reported to occur during human infection with T. cruzi.
A new lymphocyte surface protein present in normal urine. I. Isolation and physicochemical properties.
Authors: Calvanico N J , Velosa J A , Anderson W L , Tomasi T B
Published: December 2022

A lymphocyte surface glycoprotein designated urinary acidic antigen (UA) has been isolated from normal urine by a combination of preparative isoelectric focusing and ammonium sulfate precipitation. It has an m.w. of 14,000 to 17,500 daltons, and is approximately 60% carbohydrate and 40% amino acid in content. The protein exhibited the following physical properties: S20,omega = 1.24; v = 0.693 ml/g; E1%1 cm, 278 nm = 2.08; and pI-2.5. It appears to be unrelated to beta 2-microglobulin, protein HC, urinary proteose, microglobulin, or any previously described normal urine or human serum protein.
The response of murine splenic lymphocytes to concanavalin A and to co-stimulator.
Authors: Sanderson R J , Rulon K , Groeneboer E G , Talmage D W
Published: December 2022

The blastogenic and mitogenic response of murine splenic lymphocytes to concanavalin A and the response of the resulting blasts to a lymphokine co-stimulator preparation was examined with an electronic particle counting and sizing apparatus (Coulter Counter and Channelizer). Mitogenesis, as determined by increase in cell number, correlated well with the time-integrated uptake of tritiated thymidine. It was found that co-stimulator was highly mitogenic to the lectin-induced blasts, and that the cells appearing in response to it were uniformly large (co-stimulator blasts). Furthermore, the eventual increase in cell number was proportional to the co-stimulator concentration, at least for the concentrations, cell numbers, and incubation times examined. This relatively simple assay that uses the Coulter Counter and Channelizer is therefore capable of substituting for serial measurements of tritiated thymidine uptake and yields additional information on the volume spectra of responding cells, as well as forming the basis for assaying co-stimulator activity. The co-stimulator blasts were found to be capable of killing a wide variety of allogeneic as well as syngeneic concanavalin A induced blasts. The level of killing in a 3-hr 51Cr release assay varied between 9% (for the syngeneic case) and 24% of the maximum obtained by water lysis.
Stimulation of murine lymphocytes by Rauscher leukemia virus in vitro.
Authors: Bubbers J E , Elder J H , Dixon F J
Published: December 2022

Murine lymphocytes cultured with frozen and thawed Rauscher murine leukemia virus 100,000 x G supernatants demonstrated increased 3H-thymidine uptake. The stimulatory capacity co-purified with the major envelope glycoprotein, gp70, and can be specifically removed from viral supernatants by absorption with anti-gp70 antibody-linked Sepharose. Cells from all strains tested, including strains prone to autoimmune disease (MRL/1, (NZB X W)F1, NZB, and BXSB), immunologically normal strains (DBA/2, C57B1/6, BALB/c, C3H and 129/J), genetic low responders to LPS (C3H/HeJ), and mice congenitally T cell deficient (BALB/Wehi nu/nu) were equivalently responsive to viral protein stimulation. The response peaked after 3 to 4 days of culture, and cells responded at that time after brief exposure to virus supernatants at the initiation of culture. When gp70 concentrations comparable to serum levels were used, both spleen and mesenteric lymph node cells were capable of responding with stimulation indices of between 5 and 10; whereas bone marrow cells responded poorly, and neither thymocytes nor cortisone-resistant thymocytes responded. Lymphocyte stimulation was not diminished by the depletion of adherent cells, and both T- and B cell-enriched populations responded.
Heterogeneity within the population of NK and K cells.
Authors: Jensen P J , Koren H S
Published: December 2022

Using a cellular immunoadsorbant technique, we have examined the relationship between the K cell, which mediates antibody-dependent cellular cytotoxicity (ADCC) and the natural killer (NK) cell. Human peripheral blood lymphocytes (PBL) were allowed to adhere to monolayers of NK-sensitive target cells. PBL nonadherent to these monolayers and control PBL were then tested for both NK and ADCC activity by using a short-term 51Cr-release assay. The cytotoxic activity of nonadherent PBL was compared to that of control PBL by using the slope rati- method. In most cases, the extent of depletion of NK was greater than that of ADCC; however, in several experiments both activities were depleted to an equivalent extent. It is concluded that a single cell can mediate both ADCC and NK and that the selectivity of a given effector cell for NK targets depends upon the particular NK recognition site(s) that the cell bears.
The role of insulin in the response of murine T lymphocytes to mitogenic stimulation in vitro.
Authors: Snow E C , Feldbush T L , Oaks J A
Published: December 2022

The ability of insulin to influence the responsiveness of murine T lymphocytes in a culture system containing a serum substitute was documented. The presence of insulin was found to enhance the concanavalin A (Con A) reactivity of the lymphocytes. Once the cells were activated by a short-term exposure to Con A, insulin was capable of replacing Con A for the continued stimulation of the cells. This was true both for lymphocyte proliferation and for the generation of nonspecific cytotoxic T lymphocytes. The presence or absence of insulin was not found to influence the phytohemagglutinin responsiveness of the T lymphocytes. Possible reasons for the observed results are discussed in relation to a proposed model for lymphocyte activation.
Generation of hybridomas secreting murine reaginic antibodies of anti-DNP specificity.
Authors: Eshhar Z , Ofarim M , Waks T
Published: December 2022

High frequency of hybridoma lines secreting large amounts of reaginic anti-DNP antibodies were generated by the fusion of splenic lymphocytes enriched by adoptive transfer of immune cells and the NSI plasmacytoma cell line. The murine IgE molecule binds DNP with high affinity and was specifically purified by immunoabsorption. The 190,000 dalton molecule is composed of a lambda-light chain and an epsilon-heavy chain of an apparent m.w. of about 90,000. Absorption studies with anti-class-specific antisera suggest that some of the hybrid clones secrete also a mixed molecule consisting of lambda- and kappa-light chains in addition to the epsilon-heavy chain. The monoclonal reaginic antibody binds to mast cells or rat basophilic leukemia cells and, upon binding of DNP-protein, triggers an anaphylactic reaction.
T cell-mediated immunity to oncornavirus-induced tumors. I. Ly phenotype of precursor and effector cytolytic T lymphocytes.
Authors: Leclerc J C , Cantor H
Published: December 2022

Regression of tumor induced by murine sarcoma virus (MSV) is accompanied by the formation of specific cytolytic T lymphocytes (CTL). Selection of T-cells sets by Ly phenotype determination allows separation of T sets involved in the cytolytic reaction. After MSV inoculation we demonstrate that a) Ly123+ cells contain precursors of CTL, b) direct cytolysis is mainly mediated by Ly23 cells, 3) cytolytic memory is divisible into "early" memory, carried by Ly23 cells, and "late" memory, which reverts to an Ly123 precursor population, and d) Ly1 cells are required to induce anti-MSV antibody formation.
Induction of Fc epsilon-receptor bearing cells in vitro in human peripheral lymphocytes.
Authors: Yodoi J , Ishizaka K
Published: December 2022

Fc epsilon R-bearing lymphocytes were induced in vitro by the culture of peripheral lymphocytes from ragweed-sensitive patients with antigen E together with, or followed by, human IgE. Neither antigen E alone nor IgE alone induced Fc epsilon R(+) cells. As expected, culture of normal lymphocytes with the antigen and IgE failed to increase Fc epsilon R(+) cells. However, mixed lymphocyte cultures from two normal individuals responsed to human IgE for the induction of Fc epsilon R(+) cells. In both antigen-stimulated and mixed lymphocyte cultures, a portion of Fc epsilon R(+) cells induced in vitro were T lymphocytes. Evidence was obtained that Fc gamma R(+) cells are involved in the induction of Fc epsilon R(+) cells. Depletion of Fc gamma R(+) cells in the lymphocytes from ragweed-sensitive patients, before culture with antigen E and IgE, abolished the ability of the lymphocytes to respond to IgE for an increase in Fc epsilon R(+) cells.
The influence of incubation time and mitogen concentration on lymphocyte blastogenic response: determination of conditions that maximize population differences.
Authors: Bernhard M I , Pace R C , Unger S W , Wanebo H J
Published: December 2022

The blastogenic responsiveness of peripheral blood lymphocytes is a commonly applied measure of immune response capability. This assay is generally run under conditions of maximum lymphocyte stimulation. The purpose of this study was to evaluate which conditions of lymphocyte culture were able to best discriminate normal from subnormal lymphocyte responses to mitogens and antigens. Mitogen or antigen concentrations and the length of incubation time were varied while other assay conditions (serum supplement, lymphocyte concentration, amount of label, and length of label pulse) were kept constant. A total of 24 cancer patients and 25 normal controls were studied. Under optimal assay conditions that provided for maximum lymphocyte stimulation, we were unable to distinguish differences in response between young and old individuals or cancer patients and normal controls. However, at suboptimal mitogen/antigen concentrations or suboptimal incubation times, significant differences were observed in these populations. It is suggested that in the evaluation of lymphocyte stimulation responses in various clinical groups, suboptimal lymphocyte culture conditions may provide for maximum discrimination among the groups.
Ia antigen on the surface of a subfraction of T cells that bear Fc receptors for IgG.
Authors: Kaszubowski P A , Goodwin J S , Williams R C
Published: December 2022

Human peripheral blood T cells and T cell subpopulations were studied for the presence of Ia-like antigen, by using indirect immunofluorescence with heterologous rabbit anti-Ia antisera. In 13 normal subjects the percentage of T cells staining with the anti-Ia reagent was 2 to 5% and appeared limited to the T gamma subfraction. After concanavalin A (Con A) or phytohemagglutinin (PHA) activation, the proportion of Ia(+) T cells increased due to an increase in the percentage of T gamma cells bearing Ia-like antigen as well as an increase in the proportion of T gamma cells in the T cell fraction.
The influence of hapten-conjugated isologous mouse gamma-globulin as a tolerogen on H-2 restricted cytotoxic effector cells.
Authors: Waksal S D , Borel Y
Published: December 2022

Hapten-conjugated isologous mouse gamma-globulin (TNP-MGG) can induce specific unresponsiveness in spleen populations for primary antibody responses in vitro to both T-dependent (TNP-KLH) and T-independent (TNP-LPS) antigens. This was also tested simultaneously for its influence on spleen populations in the generation of cytotoxic effector cell populations to hapten-modified self. Unlike its effect on primary antibody responses (tolerogenic), TNP-MGG does not inhibit the generation of cytotoxic T cells against TNBS-treated syngeneic spleen cells. TNP-MGG was also unable to act as an immunogen in generating cytotoxic effectors against TNBS-treated spleen cells. These data show that although TNP-MGG has a tolerogenic effect on B lymphocytes (and possibly helper T lymphocytes) it does not block the generation of killer T lymphocytes directed against the hapten-modified spleen cells. A different mechanism of tolerance induction for TNP-MGG compared to hapten-modified syngeneic murine spleen is therefore suggested.
Characterization of responding cells in oxidative mitogen stimulation. II. Identification of an Ia-bearing adherent accessory cell.
Authors: Phillips M L , Parker J W , Frelinger J A , O'Brien R L
Published: December 2022

Treatment of murine lymph node or spleen cells with anti-Ia serum and complement (C), depletes the subsequent proliferative response of the residual cells to the oxidative mitogen galactose oxidase (NaGO). Restoration of the mitogenic response could be achieved by the addition of adherent accessory cells prepared by a variety of techniques. Loosely adherent dendritic cells were the most efficient population of restoring cells. Treatment of adherent cells with anti-Ia serum and C removed their capacity for restoration. Restoration of the oxidative mitogen response to lymph node cells depeleted of adherent cells by passage over nylon wool and Sephadex columns was similar to restoration of Ia- depleted lymphocyte populations. Further NaGO-induced lymphocyte transformation requires an Ly-1+2+ T lymphocyte and an Ia-positive adherent accessory cell.
Activation of the fourth component of complement (C4): assessment by rocket immunoelectrophoresis and correlation with the metabolism of C4.
Authors: Milgrom H , Curd J G , Kaplan R A , Müller-Eberhard H J , Vaughan J H
Published: December 2022

The classical pathway of complement (C) is activated in several diseases, and this activation characteristically involves the activation of C4, the fourth component of C. Since activation of C4 ultimately produces the polypeptide fragment C4d, we have applied immunoelectrophoresis in gels containing antibodies that precipitate C4d and C4 (rocket immunoelectrophoresis) as a means of detecting and quantitating C4 activation. Plasma C4 produced a single precipitin line after rocket immunoelectrophoresis, whereas plasma containing C4d produced two precipitin lines corresponding to C4d and C4. The areas enclosed by the respective precipitin line(s) were quantitated by planimetry and approximated the amounts of C4d and C4 present in the specimen. The ratio of the areas of C4d/C4 as measured in this analysis correlated significantly with the in vivo metabolism of radiolabeled C4. Our method detected C4d in the plasmas of some patients with rheumatoid arthritis, hereditary angioedema, systemic lupus erythematosus, or chronic urticaria with hypocomplementemia. These studies indicated that determination of the C4d/C4 ratio is useful in the evaluation of in vivo C activation and also may be applicable to the study and management of diseases associated with C activation.
Human leukemia-associated antigen: relation to a family of surface glycoproteins.
Authors: Pesando J M , Ritz J , Levine H , Terhorst C , Lazarus H , Schlossman S F
Published: December 2022

A heteroantiserum raised to leukemic cells of a patient with non-T cell acute lymphoblastic leukemia (ALL) has been extensively absorbed with cells from a leukemic T cell line and an autologous B lymphoblastoid cell line to produce a common ALL antiserum (CALLA). CALLA is specific for leukemic cells of most patients with non-T cell ALL and chronic myelogenous leukemia (CML) in lymphoid blast crisis. It has been extensively tested on a wide variety of normal cells and is unreactive with them. CALLA identifies a surface glycoprotein having a m.w. of approximately 100,000 on reactive cell populations. In contrast, partially absorbed anti-ALL sera detect a similar glycoprotein band on CALLA-negative B and T cell lines. The glycoprotein identified by CALLA has been isolated and used as an immunogen. This new antiserum (C129) detects a 100,000-dalton glycoprotein not only on CALLA-positive cell populations but also on most CALLA-negative normal and malignant hematopoietic cells and on B and T cell lines. We conclude that there exists a family of 100,000-dalton glycoproteins that are present on a variety of normal, transformed, and malignant cells and that possess shared as well as unique antigenic regions. The expression of at least one of these antigens, detected by CALLA, may be tumor specific.
Immunosuppressive effects of low doses of glucocorticoids: effects on autologous and allogeneic mixed leukocyte reactions.
Authors: Hahn B H , MacDermott R P , Jacobs S B , Pletscher L S , Beale M G
Published: December 2022

The effects of single oral doses of 10, 15, or 30 mg of prednisone on circulating mononuclear cells, autologous MLR, mitogen responses, and allogeneic MLR were studied in healthy volunteers. Doses as low as 10 mg were immunosuppressive, causing diminution of circulating T cells and monocytes, and significant reduction in autologous but not allogeneic MLR responses. These effects were maximal 6 hr after drug administration and gone by 24 hr. Autologous MLR responses were particularly sensitive to the effects of prednisone being significantly and consistently suppressed 2 hr after drug administration, before significant cell redistribution had occurred. Macrophage-enriched stimulating cells were more easily suppressed than responding T cells. Since the autologous MLR may be important in in vivo regulation of immune responses, its reduction by low-dose glucocorticoids may be of clinical relevance. This suppressive effect must be considered in studies of the autologous MLR in patients receiving glucocorticoid therapy.
Genetic control of the murine T lymphocyte proliferative response to collagen: analysis of the molecular and cellular contributions to immunogenicity.
Authors: Rosenwasser L J , Bhatnagar R S , Stobo J D
Published: December 2022

The genetic control of the murine immune response to denatured beef type II collagen was examined in an antigen-presenting cell-dependent T cell proliferation assay. It was found that the response to collagen is under the control of H-2-linked Ir genes, possibly operating at the level of the antigen-presenting macrophage. Utilizing in vitro cross-stimulation with synthetic collagen-like polypeptides, the data suggest that the antigenic determinants stimulating collagen immune T cells are more dependent on primary amino acid sequence and less on conformation. The implications of such findings for Ir gene specificity and other related immunologic functions is discussed.
Evidence for linked expression of latent allotypes of the heavy chain constant and variable regions.
Authors: Yarmush M L , Mandy W J , Kindt T J
Published: December 2022

CH allotypes were determined for rabbit IgG and antibody molecules identified and isolated on the basis of their expression of latent group a (VH) allotypic determinants. Serologic and chemical typing of the purified molecules revealed that five out of 10 individual preparations studied expressed d allotypes not present in the rabbit as a nominal allotype. None of the latent VH-CH combinations represented products of a new or unusual arrangement of VH and CH structural genes. This result indicates that the molecules with latent allotypes express their VH and CH allotypes in the same combinations as do their nominal counterparts and do not result from misspairing of separate genes involved in H chain synthesis.