bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro regulation of the pathogenic autoantibody response of New Zealand black mice. I. Loss with age of suppressive activity in T cell populations.
Authors: Moore J S , Calkins C E 
Published: December 2022

Abstract
An investigation of the regulation of specific anti-self responses was initiated with the development of an in vitro system in which spleen cells from NZB mice were stimulated by syngeneic mouse erythrocytes (MRBC) to produce MRBC-specific autoantibody-secreting cells. The response was measured by a modification of the focus-forming cell (FFC) assay, which enumerates cells secreting IgG, which specifically bind MRBC. Spleen cells from 9- to 12-mo-old NZB mice developed MRBC-specific FFC after 3 to 5 days in culture with MRBC. Few FFC were detected in the absence of MRBC in culture. Spleen cells from young (1- to 4-mo-old) NZB mice developed few if any FFC. Spleen cell populations containing T cells from young NZB mice suppressed this anti-MRBC response, whereas B cell populations from these young mice did not. In contrast, spleen cells, including T cell-enriched populations from old, Coombs'-positive mice were not capable under the same conditions of producing equivalent suppression of this in vitro autoimmune response. These data suggest that a population of suppressor T cells that may control the autoimmune anti-MRBC response in young NZB mice is lost, or else its activity is masked in old NZB mice that are actively producing anti-MRBC antibody.
Cloned allospecific human helper T cell lines induce an MHC-restricted proliferative response by resting B cells.
Authors: Goldberg D , Green A , Gottlieb A B , Crow M K , Lewison A , Friedman S M 
Published: December 2022

Abstract
To analyze helper T (Th) cell-induced B cell proliferation in man, we have cloned allospecific Th cells, grown them as long-term IL 2-dependent T cell lines (TCL), and analyzed their phenotypic and functional properties. The two TCL described in this report, A-7 and A-57, are both composed exclusively of T3+, T4+, T8- T cells blasts. In proliferative assays, with a panel of x-irradiated allogeneic stimulator cells, A-7 was found to proliferate in response to DR3-bearing cells, whereas A-57 responds to DR2-positive stimulators. Both TCL are capable of providing MHC-restricted polyclonal help for allogeneic B cells, as measured in the reverse hemolytic plaque assay. Of greater interest, x-irradiated A-7 and A-57 cells are capable of inducing a proliferative response by allogeneic B cells that is absolutely MHC restricted at the inductive (Th-APC) level. Thus, x-irradiated A-7 cells only trigger proliferation by DR3+ B cells, whereas A-57 cells selectively activate DR2+ B cells. In contrast, after antigen-specific activation, x-irradiated A-7 and A-57 cells can recruit a significant proliferative response by allogeneic B cells bearing "irrelevant" DR antigens. The possibility that Th-induced B cell proliferation may be restricted at the effector (Th-B cell) level was addressed by fractionating B cell populations into "activated" and "resting" subsets by discontinuous Percoll density gradient centrifugation and further purification by employing a monoclonal antibody directed against an antigen expressed on activated B cells (4F2). These studies demonstrate that activated B cells are readily and nonspecifically recruited to proliferate by activated Th cells, whereas optimal proliferative responses by resting B cells require MHC restricted Th-B cell interaction.
Cellular immunity in Q fever: modulation of responsiveness by a suppressor T cell-monocyte circuit.
Authors: Koster F T , Williams J C , Goodwin J S 
Published: December 2022

Abstract
Human infection with the rickettsia Coxiella burnetii presents as an acute flulike primary Q fever, as a subacute granulomatous hepatitis, or, rarely, as chronic endocarditis. We have previously described lymphocyte unresponsiveness to Coxiella antigen in patients with Q fever endocarditis. This unresponsiveness was antigen specific and was mediated in part by adherent suppressor cells. In this report we show that the adherent suppressor cells work via prostaglandin E2 (PGE2)4 production. Addition of the cyclooxygenase inhibitor indomethacin to cultures of PBMC from patients with endocarditis or chronic laboratory exposure resulted in consistent increases in Coxiella-specific lymphocyte proliferation. The degree of increase in proliferation induced by indomethacin correlated strongly with the amount of PGE2 produced in a 4-hr culture stimulated by Coxiella antigen, but it also correlated with the sensitivity to inhibition of mitogenesis by PGE2. The suppressor mechanism was antigen nonspecific, because induction of suppression in vitro by Coxiella antigen also suppressed Candida-induced proliferation when both antigens were present in the same culture. Addition of indomethacin to these antigen cocultures totally reversed the Coxiella-induced suppression, confirming the evidence above that the nonspecific effector mechanism of suppression was prostaglandin (PG)-mediated. Elicitation of suppression, however, was antigen specific and involved a T cell-monocyte suppressor circuit. Supernatants from Coxiella-stimulated immune T cells and from the suppressor subset (OKT8+-enriched) of those T cells, but not unstimulated immune cells, induced augmented PGE2 production by unrelated nonimmune PBMC. We conclude that the lymphocyte unresponsiveness characterizing patients with Q fever endocarditis is modulated in part by an antigen-specific T suppressor cell which secretes a lymphokine to stimulate PGE2 production by adherent cells.
Calcium requirements for increased complement receptor expression during neutrophil activation.
Authors: Berger M , Birx D L , Wetzler E M , O'Shea J J , Brown E J , Cross A S 
Published: December 2022

Abstract
It has recently been shown that human neutrophils rapidly increase surface expression of membrane receptors for C3b (CR1) and C3bi (CR3) in response to chemoattractants and other stimuli. In the present studies, we used monoclonal antibodies and flow cytometry to assess the role of Ca2+ in this process. Stimulation with ionophore A23187 in the presence of 1.2 mM Ca2+ increased CR1 330% and CR3 650% compared with unstimulated cells at 37 degrees C. Because this indicated that increasing the cytosolic free Ca2+ caused increased receptor expression, we examined the role of Ca2+ in the response to other stimuli as well. Adding 1.2 mM Ca2+ or 5 mM EDTA to the media in which the polymorphonuclear leukocytes were suspended had no effect on the CR1 response to f-MLP or LTB4, whereas Ca2+ slightly enhanced and EDTA markedly inhibited the CR3 response to these stimuli. The effects of Mg2+-EGTA and EDTA were identical. TMB-8 (200 microM), which inhibits the release of Ca2+ from intracellular stores, completely blocked the increased expression of both receptors induced by fMLP or LTB4. Increased expression of both receptors was also prevented by the calmodulin antagonists chlorpromazine (50 microM) and trifluoperazine (10 microM), but not by chlorpromazine sulfoxide. Phorbol myristate acetate (0.1 ng/ml) increased CR1 230% and CR3 265%. Again Ca2+ and EDTA did not alter the CR1 response, whereas Ca2+ increased CR3 to 287% and EDTA reduced CR3 to 187% of control. TMB-8 (250 microM) completely blocked both CR1 and CR3 responses to this stimulus as well. Thus, release of intracellular Ca2+ is necessary and sufficient for increased CR1 expression in response to diverse stimuli, but maximal increases in CR3 expression require an additional influx of extracellular Ca2+. These results indicate that the mechanisms by which the surface expression of the two different complement receptors increase are different in their requirements for extracellular Ca2+. In comparison with the work of others, we suggest that the processes of increased complement receptor expression and secretion of granular enzymes may also differ.
The helper and suppressor functions of primate T cells elicited by a 185K streptococcal antigen, as compared with the helper function elicited by a 4K streptococcal antigen.
Authors: Lehner T , Mehlert A , Avery J , Jones T , Caldwell J 
Published: December 2022

Abstract
Helper and suppressor functions of human T lymphocytes that act on antibody-forming B cells were elicited by a large 185K streptococcal cell wall antigen. However, a small 4K streptococcal peptide elicited helper but no suppressor function. These differences in the functional activities of the large and small m.w. streptococcal antigens (SA) were confirmed by direct immunisation of rhesus monkeys with the 185K-SA and 4K-SA. Sequential studies have shown that whereas the 185K-SA elicits dose-dependent helper and suppressor activities, the 4K-SA elicits only helper function. Cell-depletion studies with human cells suggest that removal of T8+ cells by killing with OK.T8 and complement leads to a loss of suppressor and a broadening in the concentration of 185K-SA, which elicits helper activity. Because the 4K-SA does not elicit suppression, removal of T8+ cells does not affect this function. However, similar depletion of T4+ cells results in loss of the helper activities, both with the 185K-SA and 4K-SA, and again a broadening in the concentration of the 185K-SA, which elicits suppression. Direct comparison by autoradiography between 125I-labeled 185K-SA and 4K-SA suggests that both antigens can bind directly to monocytes or T8+ VV+ cells. Furthermore, both antigens can induce helper function if T4+ cells are reconstituted with either monocytes or T8+ VV+ cells. Attempts will now be made to sequence the amino acid determinants of the 185K-SA, so as to define the epitopes responsible for the two major regulating functions elicited by this antigen.
Tolerance to azobenzenearsonate: idiotype-specific suppression, B cell dominance, and clonal elimination.
Authors: Collins E T , Hershey E D , Benjamin D C 
Published: December 2022

Abstract
Twenty to 70% of the antibody molecules produced by individual A/J mice in response to azobenzenearsonate (ABA) bear a particular idiotype termed the major cross-reactive idiotype (CRI). Mice that were made tolerant to ABA by injection of ABA coupled to human gamma-globulin show a decrease in production of ABA-specific antibody and a preferential loss of the major CRI. In the experiments reported here, we have used adoptive cell transfers and splenic fragment culture assays to study the mechanism(s) involved in the tolerance to ABA, with emphasis on the preferential loss of the CRI. These studies show that the decrease in total anti-ABA after the induction of tolerance is the result of a decrease in the number of ABA-responsive B cells independent of CRI expression. The preferential loss of the CRI is due to idiotype-specific T cell suppression and/or B cell dominance. In addition, it is demonstrated that immunization in the presence of idiotype-specific suppression converts a normally immunogenic stimulus into a tolerogenic signal, resulting in a decrease in the absolute number of CRI+ B cell precursors.
Bronchoalveolar cells from sarcoid patients demonstrate enhanced antigen presentation.
Authors: Lem V M , Lipscomb M F , Weissler J C , Nunez G , Ball E J , Stastny P , Toews G B 
Published: December 2022

Abstract
The recognition of foreign antigens by T lymphocytes in association with lung antigen-presenting cells may be critical in the initiation of the mononuclear alveolitis and granuloma formation of pulmonary sarcoidosis. However, it has been shown that bronchoalveolar cells (BAC) from normal volunteers function poorly as antigen-presenting cells. Therefore, the ability of sarcoid BAC to serve as accessory cells for antigen-dependent autologous T cell proliferation, as measured by tritiated thymidine uptake, was compared with that of normal BAC. Although irradiated sarcoid BAC supported antigen-induced T cell proliferation, normal BAC did so poorly (p less than 0.005). Because it has been shown that sarcoid BAC produce more interleukin 1 (IL 1) than normal BAC, it was considered that the enhancement of antigen-induced proliferative responses could result from an increased amount of IL 1, and that contaminating monocytes in the peripheral blood T cell preparations displayed the antigen for T cell recognition. Therefore, it was necessary to establish that antigen-induced T cell responses required HLA-D region compatibility between the sarcoid BAC and T lymphocytes. BAC from sarcoid patients stimulated antigen-specific proliferation in T cells lines matched for at least one HLA-D-region antigen, but failed to stimulate T cell lines that were unmatched for both antigens. This finding indicates that cells in bronchoalveolar lavage fluids from sarcoid patients were fully capable of acting as antigen-presenting cells. The identification of antigen-presenting cells in the lungs of patients with sarcoidosis together with the previous findings of activated T cells, enhanced IL 1 production, and spontaneous interleukin 2 release in sarcoid patients is compatible with the hypothesis that local cell-mediated immunity is involved in the pathogenesis of pulmonary sarcoidosis.
Isolation and characterization of My23, a myeloid cell-derived antigen reactive with the monoclonal antibody AML-2-23.
Authors: Maliszewski C R , Ball E D , Graziano R F , Fanger M W 
Published: December 2022

Abstract
In this study, we describe the isolation and characterization of My23, a human myeloid antigen defined by the monoclonal antibody (MoAb) AML-2-23. Cells of the HL-60 human promyelocytic cell line, when cultured in the presence of 1,25-dihydroxyvitamin D3 (calcitriol), express a surface protein of approximately 50 to 55 kilodaltons (Kd) which was immunoprecipitated with the AML-2-23 MoAb. Furthermore, after 2 days of exposure to calcitriol, HL-60 cells began to release My23 into culture medium, as determined by the ability of culture supernatant from these cells to block the binding of AML-2-23 to myeloid cells. My23 release was almost totally inhibited by incubation of cells at 4 degrees C, and was partially blocked by treatment of cells with cycloheximide or tunicamycin. The culture supernatant blocking factor, soluble My23, was identified as a 45 to 50 Kd protein by Western blot/immune overlay, using AML-2-23 and an 125I-labeled second antibody. My23, which was affinity-purified from culture supernatant, retained the ability to block AML-2-23 binding to myeloid cells. The affinity-purified antigen migrated on SDS-PAGE as a diffuse band in the m.w. range of 44 to 52 Kd. On treatment with endoglycosidase, the apparent m.w. of My23 decreased to approximately 40,000, indicating the presence of carbohydrate residues on My23. Serum from mice immunized with the purified antigen reacted with the same spectrum of myeloid cells as AML-2-23 MoAb, reacted with the My23 soluble protein in immunoblots, and competed with AML-2-23 for binding to myeloid cells. Binding of this antiserum to myeloid cells was blocked by cell supernatant from both monocytes and calcitriol-treated HL-60 cells, suggesting, along with results from m.w. determinations of the two preparations, that the soluble and cell surface forms of My23 are similar. Moreover, based on our finding that human plasma specifically inhibits the binding of AML-2-23 to myeloid cells, My23 may also be released in vivo. The enhanced expression of My23 on activated and more mature myeloid cells and its shedding or secretion by these cells is consistent with a functional role for My23.
Characterization of antigens and antibody specificities involved in Heymann nephritis.
Authors: Kamata K , Baird L G , Erikson M E , Collins A B , McCluskey R T 
Published: December 2022

Abstract
The present study was conducted to determine if Fx1A, a renal cortical extract used to induce Heymann nephritis, contains nephritogenic antigens in addition to the brush border-derived glycoprotein gp 330. Of 26 Lewis rats immunized with Fx1A, 24 developed abnormal proteinuria (greater than 20 mg/24 hr) by wk 10, whereas of 15 rats immunized with a partially purified gp 330 preparation (MVH), only one developed proteinuria. Immunofluorescence studies showed that all Fx1A rats developed large, diffuse, granular deposits along the glomerular basement membrane which stained brightly for IgG and C3; only 11 of the 15 MVH rats had definite deposits; in most rats, they were small and stained only moderately for IgG and faintly or not at all for C3. The Fx1A and MVH rats developed comparable levels of antibodies to MVH (gp 330) before the onset of proteinuria in Fx1A rats, after which serum IgG and antibody levels declined. In contrast, antibodies against soluble Fx1A antigens appeared earlier and rose more rapidly in Fx1A than in MVH rats. Larger amounts of IgG could be eluted from the glomeruli of Fx1A rats than from MVH rats. Eluates from the Fx1A rats contained antibodies that reacted with gp 330 and also a 95 kd antigen; the latter reactivity was not demonstrated in eluates of MVH rats. Immunoprecipitation studies showed that both gp 330 and the 95 kd antigen are components of normal glomeruli. The results show that immunization with Fx1A produces a more severe form of Heymann nephritis than does gp 330, and that Fx1A contains at least one nephritogenic antigen in addition to gp 330.
Recombinant interferon-gamma inhibits the B cell proliferative response stimulated by soluble but not by Sepharose-bound anti-immunoglobulin antibody.
Authors: Mond J J , Finkelman F D , Sarma C , Ohara J , Serrate S 
Published: December 2022

Abstract
Recombinant-derived interferon-gamma (reIFN-gamma) was found to inhibit B cell proliferation that was stimulated by soluble goat anti-mouse IgD or goat anti-mouse IgM antibodies, but not that stimulated by Sepharose-bound anti-Ig antibodies. Recombinant IFN-gamma also inhibited the BSF-1-enhanced soluble anti-Ig B cell proliferation but did not block BSF-1 enhancement of Sepharose anti-Ig-stimulated B cell DNA synthesis. Recombinant IFN-gamma concentrations as low as 0.001 U/ml were effective in suppressing the soluble anti-Ig-stimulated B cell proliferative response, and this inhibitory effect could be partially reversed by co-culture with a hybridoma anti-IFN-gamma antibody. Recombinant IFN-gamma appeared not to inhibit action of resting B cells from G0 to early G1, because it did not inhibit the increases in cell size that were stimulated by anti-delta antibody. However, it was effective in partially suppressing the anti-delta-induced increases in expression of B cell surface Ia. For reIFN-gamma to exert its maximum suppressive effect, it had to be added within the first 7 hr after the onset of culture with anti-Ig. Because reIFN-gamma is a lymphokine that can be detected in vivo, we suggest that it may play a key role in influencing physiologic B cell activation that is induced by antigens or immune complex-mediated cross-linking of surface Ig.
Functional recognition of bacterial mitogens by B lymphoma cells: reactivity of WEHI 279.1 to lipopolysaccharide and selection of nonreactive variants.
Authors: Kleine B , Coutinho A 
Published: December 2022

Abstract
To analyze functional mitogen recognition by reactive B lymphocytes, we studied the effects of bacterial lipopolysaccharide (LPS) on the growth of the WEHI 279.1 B lymphoma line (W279). We found that LPS inhibits, in a dose-dependent manner, the growth of W279 cells in culture and that it reduces the frequency of cells growing as clones under limiting dilution conditions. Furthermore, we show that differential reactivity of "wild-type" cells to increasing LPS concentrations reflects the heterogeneity in the lymphoma cell population and the frequencies of "resistant" variants to each mitogenic concentration. This allowed us to derive variant tumor cell lines and clones, no longer LPS sensitive, either from mass cultures or, in a single-step selection, under limiting dilution conditions in the presence of low and high concentrations of LPS. Although mitogen reactivity is progressively lost upon prolonged culture, resistance to LPS was found to be a stable trait in selected variants, suggesting that it results from loss of functional mitogen recognition by the reactive cells. The specificity of mitogen reactivity or resistance was shown by the fact that some of the variant clones are still reactive to T helper cell-derived factors and others are not. Thus reactivity to LPS and to T cell factors can be separated, suggesting that the cell lines described here provide new tools for the biochemical analysis of B cell activation.
The T lymphocyte response to cytochrome c. V. Determination of the minimal peptide size required for stimulation of T cell clones and assessment of the contribution of each residue beyond this size to antigenic potency.
Authors: Schwartz R H , Fox B S , Fraga E , Chen C , Singh B 
Published: December 2022

Abstract
The B10.A T cell proliferative response to pigeon cytochrome c is mainly directed against a single antigenic determinant located at the carboxy-terminal end of the molecule. In the present experiments, we used synthetic peptide analogs of the carboxy-terminal sequence of moth cytochrome c to explore the structural requirements for antigenic potency. The minimum-sized peptide capable of stimulating a full response varied with the T cell clone, but within the limits of the biological systems studied, was shown to be moth fragment 97-103. Addition of more amino acids at the amino terminal end increased the antigenic potency in uneven increments, with a large contribution being made at residue 95. Analysis of amino acid substitutions at this position provided no evidence that it contained a residue that directly contacted the T cell receptor. Instead, good agreement with an analysis that made use of helix-coil transition theory suggested that this residue, as well as others, increased antigenic potency by contributing to the stabilization of the secondary structure of the molecule in an alpha-helical configuration. The maximum effect of chain length on antigenic potency appeared to stop at residue 93, in agreement with the theoretical analysis. However, addition of several more amino-terminal residues to residue 93 showed one additional significant increment of increased potency. This was almost entirely accounted for by a single lysine located four amino acids beyond the glutamic acid at residue 93 (approximately one turn of an alpha-helix away). To experimentally test whether alpha-helix-forming tendencies could account for the increased potency of the larger analogs, the degree of helix formation in trifluoroethanol was assessed by circular dichroism measurements. A good correlation was found between antigenic potency and percentage of alpha-helix for peptides of increasing chain length from moth 95-103 up to moth 86-90; 94-103. These results suggest that secondary structure may play an important role in determining the potency of antigenic determinants involved in the activation of T lymphocytes.