bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Differences Between the Ia Antigens Determined by the I-A and I-C Subregions
Authors: Cullen Susan E. , Littman Dan R. , Schwartz Benjamin D. 
Published: December 2022

Abstract
Ia antigens isolated from radiolabeled spleen cells by immune precipitation from detergent extracts using subregion specific anti-Ia sera showed superficial structural similarity. Under nonreducing conditions, subregion-specific differences were found. The α(∼35,000 dalton) and β(∼25,000 dalton) chains of Ia molecules determined by the I-A subregion of haplotypes b, d, f, k, g, r and s were found partly in a disulfide linked form (∼58,000 daltons, “58K”) but those determined by the I-C subregion of haplotypes d, k, p and r were not linked. Reduction of isolated 58K material produced electrophoretic peaks equivalent to α and β.
The I-A determined molecules were distributed between 58K and α + β forms, and the ratio of 58K to α + β could be reduced by alkylating before detergent solubilization. It is not yet clear whether the I-A determined molecules which assume the 58K form are different from those which remain in the α + β forms.
Analysis of the Role of Phagocytic Cells in the Generation of H-2-Restricted T-Cytotoxic Effectors to Trinitrophenyl-Conjugated Proteins and Trinitrophenyl-Modified Cells
Authors: Pettinelli C. B. , Schmitt-Verhulst A.-M. 
Published: December 2022

Abstract
Mouse spleen cells cultured in the presence of trinitrophenyl-(TNP)-conjugated proteins such as bovine serum albumin (TNP25–40-BSA) generate T-cytotoxic effector cells which exhibit similar properties to those obtained by sensitization with trinitrobenzene sulfonate-(TNBS)-modified syngeneic cells. Both types of cytotoxic effectors are TNP specific and exhibit H-2K- and/or D-associated recognition.
Studies analyzing the cellular presentation of TNP-BSA indicated that TNP-BSA could be detected on the surface of TNP-BSA-preincubated spleen cells and that such cells could serve as stimulators for the generation of H-2 restricted syngeneic cytotoxic effectors. Depletion of phagocytic cells from spleen cells prior to their incubation with TNP-BSA did not affect their stimulating capacity, indicating that the interaction of the TNP-protein with the cell surface was not mediated by a phagocytic mechanism. However, when both responding and stimulating cell populations were depleted of phagocytic cells, no cytotoxic effector cells were generated either to TNP-BSA or to TNBS-syngeneic cells.
Ir Gene Control of Cytolytic T Lymphocytes Induced by TNP Modified Syngeneic Cells in Normal and Chimeric Mice
Authors: Burakoff Steven , Billings Paul , Dorf Martin , Benacerraf Baruj 
Published: December 2022

Abstract
Cytolytic T lymphocytes (CTL) generated to trinitrophenyl (TNP) modified syngeneic cells from mice bearing the H-2b,d,r,s haplotypes exhibit cytolytic activity toward TNP modified syngeneic target cells, however they also demonstrate significant levels of cross reactive lysis of TNP modified allogeneic targets. In contrast, CTL from strains bearing the H-2k haplotype are H-2 restricted, only lysing TNP modified syngeneic targets. This inability to cross-reactively lyse TNP modified allogeneic targets is a defect of the responder cell and not the stimulator. Specifically, (B6 × C3H)F1 spleen cells demonstrate cross-reactive lysis when stimulated by either TNP modified C57BL/6 or TNP modified C3H stimulator cells. Utilizing H-2 recombinant strains we have mapped the genes controlling this H-2 retriction to the K and/or IA loci. Thus, this appears to be an Ir gene-like phenomenon.
Bone marrow cells from C3H mice were allowed to mature in a lethally irradiated (B6 × C3H)F1 host to determine whether the host environment influenced CTL specificity.
Regulation of Suppressor T Cell Function Specific for Ir Controlled Antigens
Authors: Germain Ronald N. , Pierres Michel , Waltenbaugh Carl , Benacerraf Baruj 
Published: December 2022

Abstract
I-region-coded nonresponder T cell-derived suppressor extracts (TsF) specific for l-glutamic acid60-l-alanine30-l-tyrosine10 (GAT) or l-glutamic acid50-l-tyrosine50 (GT) induce T suppressor cells (Ts2) in vivo and in vitro in nonresponder spleen cells. This induction requires both an I-J subregion coded TsF and also specific antigen. The Ts2 cells are I-J+ and do not acquire these I-J determinants from passively adsorbed TsF. Further, Ts2 are highly antigen specific, being able to selectively suppress GAT vs GT-MBSA responses in the same strain. In the GT model, H-2a mice fail to produce GT-TsF, while H-2b mice cannot yield active Ts2 when exposed to GT-TsF. (B6A)F1 mice complement for GT suppression by reciprocal parental contribution of the missing suppressor components. No H-2 identity requirements for Ts2 generation by TsF have been noted in nonresponders, and Ts2 induction by nonresponder TsF can also occur in responder spleen cells, indicating lack of requirement for Ir matching between TsF donor and recipient.
Report of Ia Nomenclature Workshop Session
Authors: Sachs David H. 
Published: December 2022

Abstract
There have been three previous workshop sessions on the nomenclature of Ia antigens, each held as a special session of a larger workshop or meeting, and reports from each of these nomenclature sessions have been published (1–3). The reader is referred to these references for a detailed listing of the agreements and recommendations for Ia nomanclature reached at each of these previous sessions. The present session was held in order to review the status of Ia nomenclature, to discuss nomenclature problems that have arisen since the last such session, and to discuss the need for any possible changes in nomenclature to accommodate the rapid expansion that is still occurring in the field of Ia antigens. This report is a summary of the topics discussed.
Two Subgroups of T Helper Cells in F1 Hybrid Mice Revealed by Negative Selection to Heterologous Erythrocytes in Vivo
Authors: Sprent Jonathan 
Published: December 2022

Abstract
The specificity of heterozygous T cells for H-2-associated antigen in vivo was studied by inducing negative selection to sheep erythrocytes (SRC) in irradiated mice. Purified (CBA × C57BL/6)F1 T cells plus SRC were transferred to irradiated F1 or parental strain mice and then recovered from thoracic duct lymph 1 to 2 days later to measure T helper function. When F1 T cells were filtered with SRC through irradiated F1 mice the cells lost the capacity to stimulate anti-SRC responses by CBA, C57BL/6 or F1 B cells. The unresponsiveness was specific (normal responses were found against horse erythrocytes) and there was no evidence that suppression was involved. By contrast, F1 T cells filtered with SRC through irradiated mice of one parental strain failed to stimulate anti-SRC responses by B cells of this strain but retained the capacity to stimulate B cells of the opposite parental strain and F1 B cells. Both primed and unprimed T cells gave similar results and subsequent positive selection of the T cells to SRC in irradiated F1 mice for 5 days did not abrogate the restriction. The phenomenon was shown to be linked to the H-2 complex but not to Ig allotype.
The data provide further support for the view that F1 T cells comprise two subgroups of cells and imply that only one subgroup undergoes negative selection (is transiently withdrawn from the circulation) when exposed to antigen in irradiated mice of one parental strain. Both T cell subgroups undergo selection in irradiated F1 mice.
Quantitative Studies on the Precursors of Cytotoxic Lymphocytes
Authors: Teh H.-S. , Phillips R. A. , Miller R. G. 
Published: December 2022

Abstract
The cytotoxic response to TNP-modified syngeneic cells is small compared to the cytotoxic response to alloantigens. Limiting dilution analyses indicate that the number of lymphocytes in C57BL/6J(B6) lymph nodes responding to DBA/2J(D2) and B6-TNP are 1199 and 40 per 106 cells, respectively. These cytotoxic T lymphocytes (CL) produced as a result of stimulation of B6 lymphocytes with B6-TNP also lyse D2-TNP targets. Clonal analyses show that this cross-reactivity is a result of strong recognition of D2-TNP targets by 40% of B6-TNP specific CL and not relatively weak recognition of D2-TNP by all B6-TNP specific CL. When (C57BL/6J × DBA/2J)F1 mice (BDF1) were stimulated with BDF1-TNP, about 67% of the cytotoxic clones that lysed B6-TNP also lysed D2-TNP target cells; clones specific for either B6-TNP or D2-TNP were also produced. Cold target competition studies suggest that the higher degree of cross-reactivity in the latter case cannot be explained on the basis of the existence of antigenic specificities unique only to the F1 hybrid cells. Nor is the anomalously high F1 cross-reactivity due to the absence of parental antigenic specificities on the F1 cells. One possible explanation for these data is that the repertoire of cytotoxic precursors of the F1 hybrid for TNP-modified self antigens may be different from the sum of the repertoires for the parents.
Purification and Characterization of Mouse Brain Thy-1 Glycoprotein Antigens
Authors: Letarte Michelle , Meghji Gulzar 
Published: December 2022

Abstract
Thy-1 antigens have been isolated from C57BL/10 mouse brain. Thy-1 antigenic activity was followed during purification by measuring the rat-mouse cross-reacting determinants of the Thy-1 molecule that were recognized by a rabbit antiserum prepared against Thy-1 glycoprotein isolated from rat brain. After solubilization with deoxycholate, mouse brain Thy-1 antigens were purified by affinity chromatography to Lens culinaris lectin and by gel filtration. A 923-fold enrichment in Thy-1 activity and a 26% yield were obtained; the antigenic activity was associated with a glycoprotein of m.w. 25,000 estimated by SDS gel electrophoresis on 10% acrylamide gels.
The serologic and biochemical properties of Thy-1 molecules purified from mouse (Thy-1.2) brain were very similar to those of Thy-1 molecules purified from rat (Thy-1.1) brain and thymus. Heteroantisera produced against mouse brain Thy-1 glycoprotein detected mouse-specific as well as rat-mouse cross-reacting determinants of the Thy-1 molecule but did not discriminate between Thy-1.1 or Thy-1.2 alloantigens.
The presence of Thy-1.2 determinants on purified Thy-1 glycoprotein could be demonstrated only in the absence of detergent. In deoxycholate, monomeric Thy-1 molecules were unable to block either binding or cytoxic activity of anti-Thy-1.2 sera; after removal of deoxycholate, aggregated Thy-1 molecules could partially block the binding or the cytotoxic activity of anti-Thy-1.2 sera. Other antigenic determinants of the molecule were not affected by detergent.
Regulation of Alloantigen-Induced Cytotoxic Responses by Concanavalin A-Activated Lymphoid Cells: Suppression by Antigen Elimination
Authors: Kastner Daniel L. , Rich Robert R. 
Published: December 2022

Abstract
Spleen cells activated by concanavalin A (Con A) and subsequently irradiated with 1500 R were able to suppress the primary in vitro cytotoxic lymphocyte (CL) response of syngeneic splenocytes to H-2 disparate targets. Similarly activated and irradiated BALB/c (H-2d) splenocytes which were cultured with C57BL/6 (H-2b) stimulators for 24 hr developed cytotoxicity for H-2b, but not H-2d, tumor cell targets. This suggested that Con A-activated cells allogeneic to the stimulator might suppress the development of cytotoxic lymphocytes by eliminating antigen early in mixed leukocyte culture. This hypothesis was supported by the observation that suppression of primary cytotoxic responses was overridden by the use of greater numbers of stimulator cells. Moreover, Con A-activated (A × B)F1 lymphocytes suppressed the response of parent A to the H-2 disparate strain C to a much greater extent than they suppressed A-anti-B responses generated in such cultures. Addition of greater numbers of F1 suppressor cells did reveal a suppressive effect not readily explicable on a cytotoxic mechanism, in that modest but significant suppression of the A-anti-B response was observed. Thus, antigen elimination is a major, but not exclusive, mechanism in the suppression of CL responses by Con A-activated cells.
The Effects of Passive Immunization with Tumor-Specific Antiserum on the Active Immune Response of Mice to Sublines of Leukemia L1210
Authors: Carlson George A. , Terres Geronimo 
Published: December 2022

Abstract
In vivo, tumor cell killing was monitored with 131I-IUdR-labeled tumor cells and whole-body measurement of retained radioactivity. Treatment with antiserum in quantities that were not sufficient to kill the total leukemia cell inoculum (i.e., antigen excess) caused an immunopotentiation of the active immune response; this was manifested by an accelerated rate of tumor cell killing beginning between days 10 and 11. The results obtained in vivo were confirmed by in vitro quantitation; both the cytotoxic antibody and cell-mediated immune responses were potentiated by the injection of antiserum. Immunosuppression was also observed in passively immunized mice. Whether potentiation or suppression occurred was dependent on the relative amounts of antiserum and leukemic cells injected and the innate immunogenicity (and/or antigenicity) of the leukemic cells; antibody excess and high immunogenicity favored suppression.
Mechanism of Macrophage-Mediated Tumor Cell Cytotoxicity
Authors: Kaplan Alan M. , Brown Judith , Collins James M. , Morahan Page S. , Snodgrass Michael J. 
Published: December 2022

Abstract
Activated macrophages inhibit the incorporation of 125IUDR into the DNA of Lewis lung cells and lead to the cytotoxicity of these target tumor cells. Despite this apparent inhibition of DNA synthesis, an early increase in the number of Lewis lung (LL) cells occurs when LL is cultured with activated macrophages. This increase in the number of LL is similar to the increase in LL that occurs when LL is cultured alone or with normal macrophages for the first 18 hr of culture (approximately one doubling of cells). To resolve this apparent paradox of increased cell number without DNA synthesis, the DNA content of LL cells that were cultured with activated macrophages for 16 hr was analyzed by flow microfluorometry. These experiments indicated that subsequent to co-culture with activated macrophages, LL cells with a 50% reduction in their normal DNA content could be detected. Furthermore, after a 2-hr incubation with colcemid a &gt;95% reduction in metaphase cells occurred in LL cells cultured with activated macrophages. However, dividing nuclei without chromosome condensation appeared to be a prominent feature of these cultures. This would suggest that the genotypic or phenotypic program for cell division in the tumor cells is such that under these unique circumstances of tumor cell-activated macrophage interaction, a “reductive” cell division can proceed in the absence of DNA synthesis. We suggest that this aberrant division may be related to the lethal event that leads to activated macrophage-mediated tumor cell cytotoxicity.
Regulation of Immunoglobulin Biosynthesis in the Murine Plasmacytoma MOPC 315
Authors: Siebert Gary R. , Harris John F. , Gefter Malcolm L. 
Published: December 2022

Abstract
We have examined certain aspects of IgG biosynthesis by constructing hybrids between MPC11 (γ2b, κ) and MOPC 315 (α, λ2) that have lost the ability to synthesize one or the other heavy chain. Cells express the three chains in a stable fashion, and both autologous (parental) and heterologous (nonparental) H and L chain pairs form and are secreted. The α H chain was found in polymeric form when associated with the heterologous κ L chain. The λ2 L chain covalently assembled to the heterologous γ2b H chain. Surprisingly, autologous pairing was always favored over heterologous pairing in vivo by 5 to 10:1 in terms of rate of assembly. Similar ratios were maintained in the secreted protein. These results suggest that co-expression of particular H and L chain pairs is predetermined. Evolution presumably operates to improve antigen recognition as well as rate of assembly of active molecules.
Studies of Immunosuppression by Cobra Venom Factor
Authors: Martinelli Giorgio P. , Matsuda Takemasa , Osler Abraham G. 
Published: December 2022

Abstract
The immunosuppressive activity of CVF was evaluated in mice immunized with sheep erythrocytes and dinitrophenylated proteins. Serum antibody levels to these immunogens were estimated in activity units and on a weight basis for IgG. IgM as well as IgG antibody responses were diminished in mice pretreated with CVF. However when soluble immunogens were incorporated in CFA the suppressive effect associated with CVF was inapparent. It is suggested that C depletion per se may not fully account for the observed immunosuppression. The latter may result not only from the depression of C3 levels but also from the biologic activities of C cleavage products some of which modulate the secretory functions and state of activation of macrophages.
Functional Differentiation of B Lymphocytes in Agammaglobulinemia
Authors: Dosch Hans-Michael , Gelfand Erwin W. 
Published: December 2022

Abstract
The addition of fresh peripheral blood mononuclear cells (PBL) from four of seven patients with agammaglobulinemia to generated hemolytic plaque-forming cells (PFC) resulted in a dose-dependent suppression of PFC. This spontaneous suppressor cell activity (SSA) was restricted to the four patients who could generate a PFC response in vitro. SSA was mediated by a small subset of E-rosetting T lymphocytes characterized by theophylline-sensitive E-receptors and surface receptors for Fc-IgG. The effects of SSA were temperature dependent and reversible, and pokeweed mitogen could prevent the rapid decline of SSA observed during culture. Augmentation of SSA was achieved by agents known to increase intracellular levels of cyclic AMP, whereas lithium chloride abrogated SSA, including the drug-induced effects. Cells mediating SSA may play a role in preventing the normal transition of pre-B cells to B cells in patients with agammaglobulinemia without B lymphocytes.
Characterization of a Specific Adenosine Receptor on Human Lymphocytes
Authors: Marone Gianni , Plaut Marshall , Lichtenstein Lawrence M. 
Published: December 2022

Abstract
We have examined the mechanism of action of adenosine, a naturally occurring nucleoside that has profound effects on lymphocyte function. Adenosine (0.01 µM to 10 µM) increased lymphocyte cAMP levels in a dose-dependent fashion with a maximal (10 µM) increase of about 4-fold, whereas adenine, guanosine, and inosine had no effect on lymphocyte cAMP levels at concentrations of 100 µM. Adenosine appears to act on the cell surface since 1) 2-chloroadenosine, a poorly metabolized adenosine analogue, was as active as adenosine and 2) dipyridamole, which markedly inhibited [3H]-adenosine uptake by human lymphocytes, did not affect adenosine-induced accumulation of cAMP.
The specificity of the adenosine effect was established by showing that the methylxanthine derivatives, theophylline and 3-isobutyl-1-methylxanthine (IBMX), specifically block the accumulation of cAMP in lymphocytes induced by adenosine. Theophylline is a competitive inhibitor of the effect of adenosine, with an estimated dissociation constant of theophylline-receptor complex of about 6.3 × 10-7 M. The results suggest that adenosine increases the intracellular cAMP content of lymphocytes as a result of its interaction with a specific membrane receptor which results in the activation of adenylate cyclase.
Stimulation of Mitogenic Responses in Human Peripheral Blood Lymphocytes by Lipopolysaccharide: Serum and T Helper Cell Requirements
Authors: Miller Richard A. , Gartner Suzanne , Kaplan Henry S. 
Published: December 2022

Abstract
Stimulation of human peripheral blood lymphocytes by lipopolysaccharide (LPS) was studied by the incorporation of 3H-thymidine. Peak stimulation occurred at 7 to 9 days over a broad range of LPS concentrations. Both Escherichia coli and Salmonella typhimurium LPS were effective mitogens with S. typhimurium having slightly higher activity. There was a strict serum requirement; pooled fresh frozen human serum was found to best support stimulation. In fetal calf serum, LPS caused a reduction in culture-induced stimulation. Cell separation procedures were employed in order to study the nature of the responding cell population. It was found that only non-T cells were stimulated by LPS, but in order for maximal stimulation to occur there was a requirement for helper T cells.
T Cell Regulation of Specific B Cell Responses
Authors: Campos-Neto Antonio , Levine Herbert , Schlossman Stuart F. 
Published: December 2022

Abstract
The role of T cells in the generation of specific antibodies to antigens under Ir gene control was investigated in strain 2 guinea pigs. The specificity of anti-α,Dnp-Lys9 antibody was studied in guinea pigs with intact immune responses and in strain 2 guinea pigs deprived of T cells by adult thymectomy, lethal irradiation, and reconstitution with syngeneic bone marrow cells. Conventional strain 2 guinea pigs developed both T cell responses and highly specific anti-α,Dnp-Lys9 antibody. In contrast, strain 2 “B” guinea pigs failed to develop delayed hypersensitivity and in vitro T cell responses. Nevertheless, these “B” guinea pigs could produce anti-Dnp antibody of restricted heterogeneity and in quantities comparable to those produced by the conventional strain 2 guinea pigs. It was shown that anti-α,Dnp-Lys9 antibody produced in strain 2 “B” guinea pigs lacking specific T cell responses could not distinguish α,Dnp-Lys9 from dinitrophenol. Similar antibodies are produced in strain 13 guinea pigs that are poly-L-lysine, Ir gene negative. Reconstitution of strain 2 “B” guinea pigs with normal T cells enabled them to develop both cell-mediated immune responses and antibody of highly discriminatory power. These findings support the notion that in the absence of specific T cells, comparably specific B cell antibody responses cannot be generated, and perhaps more importantly, that specific T cells are required to facilitate the amplification of unique B cell clones.
Natural Cell-Mediated Cytotoxicity in Guinea Pigs: Properties and Specificity of Natural Killer Cells
Authors: Altman Amnon , Rapp Herbert J. 
Published: December 2022

Abstract
Lymphoid cells of guinea pigs were found to be naturally cytotoxic against a variety of target cells. Natural killer (NK) cell activity was high in peripheral blood and spleen, low in lymph nodes and peritoneal exudates, and absent in the thymus. Significant activity was found between the ages of 3 and 40 weeks, and strain 2 guinea pigs had a higher NK activity than strain 13 guinea pigs. Peripheral blood NK cells were sensitive to treatment with ammonium chloride solution, whereas splenic NK cells were resistant to the same treatment. The NK cells were found to be nonadherent to nylon wool and plastic and were enriched among cells bearing receptors for the Fc portion of IgG. The NK activity of guinea pig lymphocytes was selective in that only some, but not all, of the target cells used were susceptible to the cytotoxic effector cells. Susceptible target cells included syngeneic, allogeneic, and xenogeneic tumor cell lines, especially the human myeloid cell line K562, and some passages of primary syngeneic fibroblast cultures. A positive correlation was found between the direct susceptibility of different targets to NK cells and their ability to inhibit competitively the killing of K562 target cells. The NK cells in guinea pigs appear to be similar to human NK cells in several aspects and may, therefore, serve as a useful model for studying certain aspects of human NK activity.