bluuebunny/crossref_metadata_2025_split huggingface dataset:
An immunogenic antigen of murine Plasmodium yoelii 17X associates with class I MHC glycoproteins.
Authors: Mogil R J , Patton C L , Green D R 
Published: January 2023

Abstract
Reticulocytes infected with the non-lethal variant of Plasmodium yoelii 17X (PY17X-NL) express elevated levels of class I, but not class II, MHC Ag when compared with non-parasitized reticulocytes. In contrast, class I Ag are not detectable on erythrocytes parasitized by the lethal variant PY17X-L. In addition, the responder status of various inbred strains of mice to PY17X-NL has been shown to positively correlate with the levels of class I MHC antigens expressed on PY17X-NL parasitized red blood cells (PRBC). MHC Ag are known to restrict, or guide, immune responses. However, earlier studies have failed to demonstrate H-2 restricted activity in the effector arm of immunity to blood-stage murine malaria. Therefore, we have examined the induction of immunity by irradiated PY17X-NL PRBC. No MHC restriction was observed in the ability of PRBC to immunize recipients. However, using irradiated PRBC bearing low, intermediate or high levels of class I Ag we found that the levels, rather than haplotype, of class I Ag expressed on irradiated PRBC greatly influenced their ability to induce immunity. Furthermore, class I-associated parasite-directed Ag were isolated as an immunogenic complex with anti-class I MHC antibody. Such complexes induced immunity in vivo in the absence of adjuvant suggesting a biologically important mechanism by which non-lethal, reticulocytic forms of malarial parasites may immunize their hosts.
The major concanavalin A-binding surface glycoprotein of Leishmania donovani chagasi promastigotes is involved in attachment to human macrophages.
Authors: Wilson M E , Hardin K K 
Published: January 2023

Abstract
Leishmania donovani, the protozoan causing visceral leishmaniasis, is an obligate intracellular parasite of mammalian macrophages. Considerable evidence has suggested that the ingestion of L. donovani promastigotes by macrophages occurs via receptors on the surface of the phagocyte. During this study, a glycoconjugate that may be involved in the receptor-mediated ingestion of L. donovani chagasi promastigotes was isolated from the parasite membrane. Octyl glucoside-soluble extracts of promastigote membranes contained a predominant doublet migrating at 60 kDa, seen by SDS-PAGE. The 60-kDa molecule was the major externally disposed promastigote surface protein labeled by 125I, and it was the major Con A-binding protein on L. donovani chagasi, as determined by Con A binding to parasite proteins transferred to nitrocellulose. Attachment of promastigotes to human monocyte-derived macrophages was inhibited by varying concentrations of the membrane extract containing both proteins, and adsorption of extracts on Con A-Sepharose resulted in both removal of the 60,000 Mr glycoprotein and loss of the ability of extracts to inhibit promastigote attachment to human macrophages. After further purification of the 60-kDa glycoprotein by gel filtration, its inhibitory activity increased 45-fold over the unpurified membrane extract. Examination of Con A blots of stationary phase promastigotes isolated from an infected hamster revealed a marked loss in the major Con A-binding glycoprotein over 4 mo in in vitro culture after isolation from the rodent host, corresponding to a loss in infectivity of the promastigotes for hamsters. The results suggest that the major Con A-binding surface glycoprotein from L. donovani chagasi promastigotes is important in attachment to human macrophages, and may be a factor in parasite virulence for a mammalian host.
Two signals are required for accessory cells to induce B cell unresponsiveness. Tolerogenic Ig and prostaglandin.
Authors: Schad V C , Phipps R P 
Published: January 2023

Abstract
We previously demonstrated that a lymphoid dendritic cell-like tumor line (P388AD.2) presented a normally tolerogenic signal, fluoresceinated sheep gamma-globulin (FL-SGG), as an immunogenic one. In contrast, macrophages derived from the peritoneal cavity potentiated the ability of FL-SGG to induce B cell unresponsiveness. In this paper we examined whether two different Ia+ splenic accessory cells differentially presented tolerogen to spleen cells or fluorescein (FL)-binding B cells. Interestingly, lymphoid dendritic cells presented FL-SGG to spleen cells and elicited augmented anti-FL antibody responses, whereas splenic macrophages presented this same moiety and elicited hapten-specific B cell unresponsiveness. The mechanism of splenic macrophage-elicited B cell negative signaling was investigated, and it was found that B cell unresponsiveness was abrogated in the presence of the cyclooxygenase inhibitor indomethacin. This observation suggested a crucial role for PG in B cell negative signaling. The addition of 10 nM PGE2 restored unresponsiveness in cultures treated with indomethacin and tolerogen-pulsed macrophages, even though this dose of PG had no effect on the ability of B cells to be triggered by an immunogenic signal. A role for T cells was excluded, inasmuch as purified hapten-specific B cells were specifically tolerized by FL-SGG-pulsed macrophages. Lymphoid dendritic cells pulsed with FL-SGG did not deliver a tolerogenic or immunogenic signal to FL-specific B cells. However, when PGE2 was supplied, B cell unresponsiveness was induced. Finally, we tested whether "non-tolerogenic" doses of FL-SGG could render hapten-specific B cells unresponsive in the presence of PGE2, but in the absence of accessory cells. Interestingly, the combination of non-tolerogenic amounts (10 to 1000 pg/ml) of FL-SGG in conjunction with PGE2 induced unresponsiveness, whereas neither moiety alone was effective. These results suggest that splenic macrophages and lymphoid dendritic cells exert opposing effects on the immune system as evidenced by the induction of negative or positive B cell signaling. Our observations suggest that one of the key factors in controlling whether an accessory cell delivers a tolerogenic signal is the ability to secrete PG.
Immunologic abnormality in NZB/NZW F1 mice. Thymus-independent occurrence of B cell abnormality and requirement for T cells in the development of autoimmune disease, as evidenced by an analysis of the athymic nude individuals.
Authors: Mihara M , Ohsugi Y , Saito K , Miyai T , Togashi M , Ono S , Murakami S , Dobashi K , Hirayama F , Hamaoka T 
Published: January 2023

Abstract
Both NZB nu/+ and NZW nu/+ mice were microbially clean by cesarean section. The (NZB x NZW)F1 hybrid (NZB/W) nu/nu mice and nu/+ littermates were then generated by mating of NZB nu/+ with NZW nu/+mice under specific pathogen-free conditions. The female NZB/W F1 nu/nu mice did not develop autoimmune kidney disease, whereas all of nu/+ female littermates mice exhibited proteinuria and died of renal failure with a 50% survival time of 35 wk. Namely, nude mice had no signs of proteinuria up to the time of their death caused by other diseases rather than glomerulonephritis, and their mean survival time was greater than 45 wk. Nude mice had also no anti-ssDNA antibody in their serum. However, splenic B cells of NZB/W nude mice exhibited hyper-responsiveness to both LPS and B151-TRF2, a T cell-derived polyclonal B cell-stimulation factor, and produced large numbers of Ig-secreting cells and anti-TNP plaque-forming cells as well as anti-ssDNA antibody comparable to the nu/+ littermate mice. Interestingly, thymus-engrafted NZB/W nude mice developed autoimmune disease exemplified by the induction of anti-ssDNA antibody and proteinuria at approximately the same time as their nu/+ littermates. These results indicate that the B cell hyper-responsiveness found in NZB/W mice is apparently determined by the T cell-independent process, and T cells are obligatorily required for the development of autoimmune disease in NZB/W mice.
Regulation of the immune response by sex hormones. I. In vitro effects of estradiol and testosterone on pokeweed mitogen-induced human B cell differentiation.
Authors: Sthoeger Z M , Chiorazzi N , Lahita R G 
Published: January 2023

Abstract
Sex hormones have been implicated in the pathogenesis of many autoimmune disorders, presumably through regulatory influences on the immune system. However, the mechanisms of sex steroid action on humoral and cellular immune responses are not precisely understood. In this study, the in vitro effects of physiologic concentrations of 17 beta-estradiol and testosterone on the Ag non-specific differentiation of human PBMC were examined using optimal and sub-optimal doses, respectively, of PWM. In cultures of PBMC from 14 normal donors (7 men and 7 women, aged 25 to 45 yr), 17 beta-estradiol (0.5 to 30 ng/ml) enhanced PWM-induced generation of PFC by 46% (p less than 0.01), whereas testosterone (10 to 300 ng/ml) inhibited PFC generation by a mean of 36% (p less than 0.001). The enhancing and suppressing effects of the sex steroids on PBMC occurred early inasmuch as estradiol and testosterone had to be added to the cultures at their initiation (6 and 24 h, respectively) in order to observe their influence. Moreover, deletion of the hormones from the cultures after as short a period as 12 h did not obviate their effects. There was no alteration of the kinetics of the response to PWM or an effect on the number of spontaneous PFC generated in vitro in the absence of PWM. In addition, there was no difference among men and women in response to either sex steroid, and within the female group, no variation was observed on different days of the menstrual cycle. These studies demonstrate direct immunoregulatory effects of specific sex steroids on human PBMC and support the idea that these hormones may have a role in the pathogenesis and treatment of some autoimmune disorders.
Spontaneous cytotoxicity and tumor necrosis factor production by peripheral blood monocytes from AIDS patients.
Authors: Wright S C , Jewett A , Mitsuyasu R , Bonavida B 
Published: January 2023

Abstract
Peripheral blood monocytes (PBM) from AIDS patients have exhibited defects in some but not all of the immune functions yet tested. This study has examined the capacity of AIDS PBM to lyse tumor target cells as well as their ability to secrete TNF. Untreated PBM from AIDS patients were significantly cytotoxic to U937 target cells and responded to IFN-gamma pretreatment with augmented cytotoxicity. Both the spontaneous and IFN-gamma-stimulated cytotoxic activity was significantly (p less than 0.01) higher than that observed with normal PBM. The cytotoxic activity depended on the E:T ratio used and was higher in AIDS PBM at all ratios tested (10:1 to 40:1). Because TNF has been implicated in macrophage cell-mediated cytotoxicity, we examined whether the elevated cytotoxic activity of AIDS PBM was associated with an increase in TNF production. Supernatants from PBM cultured overnight with or without IFN-gamma were tested in a bioassay measuring cytotoxicity against U937 target cells as well as in an RIA specific for TNF. Supernatants derived from either unstimulated or IFN-gamma-treated AIDS PBM exhibited significantly higher levels of cytotoxicity than supernatants from normal macrophages. Both normal and AIDS PBM produced higher levels of cytotoxic factors in response to IFN-gamma. As determined by the RIA, AIDS PBM spontaneously released high levels of TNF whereas little TNF was produced by normal PBM. Treatment with IFN-gamma augmented the level of TNF production in both AIDS and normal PBM. These results demonstrate that PBM from AIDS patients have undergone in vivo activation as manifested by both cytotoxicity against tumor target cells and production of TNF. Target cell lysis by both AIDS PBM and their supernatants was inhibited by monoclonal anti-rTNF, suggesting that the increase in PBM cell-mediated cytotoxicity was caused by an increase in TNF production. The significance of these findings in the pathogenesis of the disease is discussed.
Membrane IgM and IgD molecules fail to transduce Ca2+ mobilizing signals when expressed on differentiated B lineage cells.
Authors: Justement L B , Wienands J , Hombach J , Reth M , Cambier J C 
Published: January 2023

Abstract
We have measured Ca2+ mobilization in a panel of B lineage cell lines after stimulation with anti-Ig to assess whether membrane Ig transduces a functional signal in cells that are representative of immature, mature, or terminally differentiated stages. For these studies, three transfected cell lines which express the same IgM molecule (300-19 microns lambda 36/8, K46-17 microns lambda, and J558L microns lambda 3) as well as two lines expressing an identical IgD molecule (K46 delta m2.6 and J558L delta m8.8) were used. Cross-linking of membrane Ig on IgM+ or IgD+ lymphomas (K46-17 microns lambda or K46 delta m2.6) resulted in a Ca2+ mobilization response that is similar to that seen in mature, resting B cells. Both intracellular release and extracellular influx of Ca2+ were observed. In contrast, ligation of membrane Ig on an IgM+ pre-B cell line (300 - 19 microns lambda 36/8) induced extracellular influx of Ca2+ but no detectable intracellular release. Finally, cross-linking of membrane Ig on IgM+ or IgD+ plasmacytomas (J558L microns 3 or J558L delta m8.8) or an IgD+ B cell hybridoma (B1.8.delta 1) expressing an endogenous Ig gene, did not result in a detectable Ca2+ mobilization response. Importantly, stimulation of cells with the GTP-binding protein activator, aluminum fluoride, resulted in a comparable Ca2+ mobilization response in all cell lines. In view of the fact that aluminum fluoride induced a Ca2+ response in the terminally differentiated B cell lines, J558L microns 3, J558L delta m8.8, and B1.8.delta 1, it is likely that there is an alteration in the signal transduction cascade at some point proximal to GTP binding protein activation. This finding suggests that differentiation of the B cell is accompanied by the loss or alteration of one or more components that couple membrane Ig to subsequent signal transduction elements. Finally, it has previously been demonstrated that the IgM+ cell lines described above, express the recently described membrane Ig-associated protein, B34. Thus, it is apparent based on the fact that the J558L microns 3 cell line does not mobilize Ca2+ after stimulation with anti-Ig, that coexpression of B34 in association with membrane Ig does not constitute a functional receptor complex capable of activating GTP-binding proteins that in turn regulate Ca2+ mobilization.
Activation-induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation.
Authors: Shi Y F , Szalay M G , Paskar L , Sahai B M , Boyer M , Singh B , Green D R 
Published: January 2023

Abstract
Some T cell hybridomas, upon activation via the TCR, rapidly undergo cell death. In this paper, we demonstrate that this activation-induced cell death (AICD) is accompanied by morphologic changes seen at the electron and light microscopy levels. The most striking changes are an extensive condensation of the chromatin and formation of membrane blebs. In addition to the morphologic changes, a significant portion of genomic DNA is broken at an interval of approximately 200 bp, producing a ladder of oligonucleosome-sized fragments after gel electrophoresis. Taken together, these observations indicate that AICD proceeds via apoptosis, or programmed cell death. This is additionally supported by the observation that AICD-associated phenomena are at least partially inhibited by cycloheximide or actinomycin D. Curiously, AICD and its associated DNA fragmentation are completely inhibited by aurintricarboxylic acid, a known nuclease inhibitor. The possible relationship between AICD in vitro, and the negative selection process (wherein selection may proceed via AICD of developing, autoreactive thymocytes) is discussed.
Human B lymphocytes define an alternative mechanism of adhesion to fibronectin. The interaction of the alpha 4 beta 1 integrin with the LHGPEILDVPST sequence of the type III connecting segment is sufficient to promote cell attachment.
Authors: Garcia-Pardo A , Wayner E A , Carter W G , Ferreira O C 
Published: January 2023

Abstract
In this report we have studied the mechanism of human B lymphocyte adhesion to fibronectin and to proteolytic fragments of this protein. B cells adhered to fibronectin and to a 38-kDa fragment, derived from the A chain, containing the Hep II domain and most of the type III connecting segment, IIICS, of fibronectin. Cells did not bind to an 80-kDa fragment containing the RGD adhesive sequence of fibronectin. Attachment to fibronectin or to the 38-kDa fragment was not affected by the 80-kDa fragment, the GRGDSPC synthetic peptide, or by a mAb specific for the alpha chain of the RGD-dependent fibronectin receptor, alpha 5 beta 1. However, B cell adhesion to fibronectin was inhibited by the synthetic peptides CS-1, comprising the first 25 amino acids of IIICS and B12, containing the sequence LHGPEILDVPST of CS-1 (residues 14-25). Moreover, this sequence was shown to be sufficient to induce stable cell adhesion when coated on plastic surfaces. A mAb specific for the alpha-subunit of the alpha 4 beta 1 integrin, completely inhibited B cell attachment to B12, CS-1, 38 kDa, and fibronectin coated substrata. These data clearly indicate that adhesion of B lymphocytes to fibronectin is exclusively mediated by the interaction of alpha 4 beta 1 with residues 14-25 of the IIICS region in fibronectin. Therefore this interaction constitutes an alternative pathway of adhesion to fibronectin, independent of RGD and alpha 5 beta 1.
Studies of cloned simian immunodeficiency virus-specific T lymphocytes. gag-specific cytotoxic T lymphocytes exhibit a restricted epitope specificity.
Authors: Yamamoto H , Miller M D , Tsubota H , Watkins D I , Mazzara G P , Stallard V , Panicali D L , Aldovini A , Young R A , Letvin N L 
Published: January 2023

Abstract
CD8+ CTL inhibit the replication of HIV and simian immunodeficiency virus of macaques (SIVmac) in PBL and, therefore, are likely to play an important role in containing the spread of the AIDS virus in infected individuals. We have generated a series of gag-specific lytic T lymphocyte clones from PBL: of an SIVmac-infected rhesus monkey. These T cell clones are CD3+CD8+ and are MHC class I-restricted in their target specificity. They are, therefore, CTL. Interestingly, all gag-specific CTL clones, as well as the gag-specific lytic activity of PBL of this monkey, demonstrated specificity for a single 25 amino acid fragment of the SIVmac gag protein. Moreover, they were restricted in their lytic function by a single MHC class I allele. These findings illustrate a powerful method for cloning AIDS virus-specific T lymphocytes and demonstrate a remarkably restricted epitope specificity of this AIDS virus-specific CTL response.
Regulation of macrophage activation by IL-3. II. IL-3 and lipopolysaccharide act synergistically in the regulation of IL-1 expression.
Authors: Frendl G , Fenton M J , Beller D I 
Published: January 2023

Abstract
We have previously reported that IL-3, a cytokine produced by both Th1 and Th2 type CD4+ T cells, displays macrophage-activating potential. IL-3, like IFN-gamma, readily induced functions related to Ag presentation (e.g., Ia and lymphocyte function-associated Ag-1 expression). However, in contrast to the response elicited by IFN-gamma, tumor cytotoxicity was not induced by IL-3. In this paper we have evaluated the capacity of IL-3 to regulate IL-1 expression. Our data demonstrate that although IL-3 alone was unable to induce the production of substantial IL-1 bioactivity in peritoneal exudate cells, it contributed synergistically to the induction of IL-1 bioactivity in the presence of suboptimal doses of LPS. It was of interest that IFN-gamma, which can also interact synergistically with LPS, was unable to complement the partial signals provided by IL-3 for the expression of IL-1 bioactivity, suggesting that IL-3 and IFN-gamma may be providing similar stimulatory signals in this respect. Our studies on the mechanism of synergy between IL-3 and LPS indicated that the effect of LPS did not appear to be mediated by the well-characterized LPS-inducible cytokines of macrophage origin (i.e., IL-1, alpha and beta, TNF-alpha, and IL-6). The best characterized function of IL-3 is its multicolony-stimulating activity as a CSF; in this context we also studied granulocyte-macrophage CSF and noted that it behaves similarly to IL-3 in that it can synergistically contribute to IL-1 induction. A similar, but more dramatic induction of IL-1 synthesis in response to IL-3 was demonstrated by the P388.D1 murine macrophage cell line. The kinetics and the molecular mechanism of the response of P388.D1 to IL-3 indicate several unique features of IL-3-induced IL-1 expression: 1) IL-3 itself induced IL-1 mRNA expression, which was unaccompanied by substantial production of bioactivity, either cell-associated or secreted into the culture supernatant; 2) IL-3 synergized with suboptimal doses of LPS to induce not only heightened IL-1 mRNA levels but bioactivity as well; and 3) IL-3, when combined with LPS, altered the kinetics of IL-1 message and bioactive protein production in response to LPS: IL-3 and LPS induced an early release (3 to 7 h poststimulation) of the IL-1 protein as well as a second peak of mRNA and bioactivity (at 12 to 36 h), which was not observed in response to either IL-3 or LPS alone.(ABSTRACT TRUNCATED AT 400 WORDS)
Selective elimination in vitro of alloresponsive T cells to human transplantation antigens by toxin or radionuclide conjugated anti-IL-2 receptor (Tac) monoclonal antibody.
Authors: Kozak R W , Fitzgerald D P , Atcher R W , Goldman C K , Nelson D L , Gansow O A , Pastan I , Waldmann T A 
Published: January 2023

Abstract
The human allogeneic mixed lymphocyte reaction is the in vitro correlate of graft rejection. Cytotoxic effector cells generated during an allogeneic mixed lymphocyte reaction were previously shown to express the human p55 IL-2 receptor subunit, whereas resting cells do not express this receptor peptide. In this study, we asked whether Pseudomonas exotoxin or bismuth-212 (an alpha-particle emitting radionuclide) coupled to the anti-IL-2 receptor mAb, anti-Tac, were able to selectively eliminate alloresponsive cells generated during an allogeneic mixed lymphocyte reaction. After assembly, anti-Tac immunoconjugates retained their binding integrity, specificity, and selectivity. Deletion of alloresponsive cells was shown by the removal of alloproliferating cells as assessed by quantitating cell recovery and by measurement of thymidine incorporation into newly synthesized DNA. Both toxin and radionuclide immunoconjugates eliminated established cytotoxic effector cells generated in an allogeneic mixed lymphocyte reaction, while leaving intact the PHA-inducible mitogenic response of the nonactivated cells. The addition of excess anti-Tac blocked all of the effects of these cytotoxic reagents. The therapeutic reagents in vitro were most effective when added just prior to the peak of the alloproliferative response, when receptor expression would be close to maximum. Thus, anti-Tac conjugated either with toxin or radionuclide is effective in vitro in specifically eliminating cytotoxic effector cells.