bluuebunny/crossref_metadata_2025_split huggingface dataset:
Requirements for stimulation of autoreactive T cells by thymic stroma.
Authors: Burstyn D , Zauderer M 
Published: December 2022

Abstract
Thymic stromal cells are more efficient than similarly treated spleen cells for Ag presentation to Ag-specific, MHC-restricted T cell lines. Thymic stromal cells fail, however, to stimulate proliferation of autoreactive T cell lines. This failure to stimulate autoreactive T cells does not appear to be due to tolerance induction because thymic stroma does not interfere with subsequent stimulation by spleen cells. Moreover, the ability of thymic stromal cells to stimulate autoreactive T cells can be restored by addition of exogenous IL-1. This demonstrates that the specific self-determinants recognized by autoreactive T cells can be expressed on thymic stromal cells. Failure of stimulation by thymic stromal cells in the absence of exogenous IL-1 may reflect a difference in the physiologic requirements for activation of autoreactive T cells as compared to Ag-specific, MHC-restricted T cells.
Functional sites on the A alpha-chain. Polymorphic residues involved in antigen presentation to insulin-specific, Ab alpha:Ak beta-restricted T cells.
Authors: Reske-Kunz A B , Landais D , Peccoud J , Benoist C , Mathis D 
Published: December 2022

Abstract
The interaction between the clonally selected TCR, the processed Ag peptide and the Ia molecule is not fully understood in molecular terms. Our study intended to delineate the residues of Ab alpha molecules that function as contact sites for Ag and for the TCR of a panel of T cells specific for the A chain of insulin in combination with mixed haplotype Ab alpha:Ak beta molecules. Multiple L cell transfectants expressing alpha,beta-heterodimers composed of wild-type A beta- and chimeric or mutant A alpha-chains served as antigen presenting cells. The recombinant A alpha-chains had been generated by an exchange of allelically hypervariable regions (ahv) or amino acids. The results point out a broad spectrum of b sequence requirements for the bovine insulin-specific activation of the various T cell populations. Activation of some T cells seemed quite permissive, requiring b-haplotype amino acids in any one of the three ahv, while others had strict requirements, demanding b-haplotype sequence in all three ahv. Our data stress the role of ahvII and especially ahvIII in T cell activation. Interestingly, single amino-acid substitutions in ahvII or ahvIII of Ak alpha were sufficient to bring up full stimulation potential for two T cell hybridomas. We also found that some ahv permutations influenced the Ag preference (beef insulin versus pig insulin) of some T cells. These data suggest a critical role for the three-dimensional structure of the complex formed by Ia and the processed Ag peptide. The stability of the trimolecular complex essential for T cell activation is envisioned as being the sum of the interactions between Ag/I-A, TCR/Ag, and TCR/I-A, each variable in strength and compensated for by the others.
IL-4 induces LFA-1 and LFA-3 expression on Burkitt's lymphoma cell lines. Requirement of additional activation by phorbol myristate acetate for induction of homotypic cell adhesions.
Authors: Rousset F , Billaud M , Blanchard D , Figdor C , Lenoir G M , Spits H , De Vries J E 
Published: December 2022

Abstract
LFA-1 and LFA-3 expression is absent or low on Burkitt's lymphoma cell lines and low on the EBV-transformed B cell line UD61. Incubation of cells of BL2 and of UD61 with various concentrations of IL-4 resulted in induction of LFA-1 and LFA-3 expression in a dose dependent fashion. This effect was already observed after 16 h of incubation whereas maximal expression was obtained after 72 h. Induction of LFA-1 and LFA-3 expression seemed to be specific for IL-4, because IL-1, IL-2, IL-3, IFN-alpha, IFN-gamma and a low m.w. B cell growth factor were ineffective. LFA-1 and LFA-3 induction by IL-4 was blocked specifically by an anti-IL-4 antiserum. Induction of LFA-1 expression by IL-4 was furthermore confirmed at the specific LFA-1 beta-chain mRNA level. IL-4 was unable to induce LFA-1 expression on EBV-transformed lymphoblastoid cell lines of two LFA-1-deficient patients. BL2 grows as single cells, but induction of LFA-1 and LFA-3 expression by IL-4 was insufficient to induce homotypic cell adhesions and required PMA as a second signal. PMA alone did not induce LFA-1 antigen expression and was unable to induce adhesions between BL2 cells in the absence of IL-4 in 22 h assays. Addition of PMA to BL2 cells that expressed LFA-1 Ag upon incubation with IL-4 resulted in aggregate formation within 30 min. Adhesions between BL2 cells induced by IL-4 in combination with PMA were blocked by anti-LFA-1 beta or anti-LFA-1 alpha-chains mAb. In addition, these mAbs dispersed preformed aggregates of BL2 cells. Our results indicate that IL-4 can induce the adhesion molecules LFA-1 and LFA-3 on B cell lines, but that an additional activation signal provided by PMA was required for the induction of homotypic cell adhesions.
Pretreatment of cloned helper T lymphocytes with IL-2 induces unresponsiveness to antigen and concanavalin A, associated with decreased inositol phosphate and diacylglycerol production.
Authors: Schell S R , Fitch F W 
Published: December 2022

Abstract
IL-2 pretreatment of cloned Th lymphocytes has been demonstrated to render these cells unresponsive to subsequent stimulation through the TCR. These cells remain unresponsive for up to 7 days after removal from IL-2. Cells rendered unresponsive to Ag by pretreatment with IL-2 also demonstrated reduced increases in intracellular calcium ([Ca2+]i) after stimulation, hence this unresponsiveness is believed to result from absence of sufficient [Ca2+]i for activation of lymphokine genes. We have confirmed these observations, and demonstrate that only that portion of the [Ca2+]i increase derived from extracellular sources is inhibited in IL-2 pretreated cells. Further, inositol degradation and diacylglycerol production after stimulation are observed to be markedly reduced in cells rendered unresponsive by IL-2 pretreatment, suggesting that signal transduction leading to cleavage of phosphatidylinositol 4,5-bisphosphate after Ag receptor engagement is incomplete in these cells. However, treatment of IL-2 pretreated cells with AlF4- results in both production of inositol phosphates as well as increased intracellular calcium, suggesting that phospholipase C remains active in these cells. It appears that chronic IL-2 exposure regulates Th activation by inhibiting the signal transduction which follows engagement of the TCR.
Collagen-induced arthritis in Biozzi mice. Joint involvement is not correlated with collagen II IgG2a autoantibodies nor restricted to only H-2q and H-2r.
Authors: Bouvet J P , Couderc J , Bouthillier Y , Franc B , Decreusefond C , Mouton D 
Published: December 2022

Abstract
High (H) and low (L) immune responder "Biozzi" mice, obtained by four different selections, were investigated for their ability to develop collagen-induced arthritis. Both LI and LII lines--characterized by their low antibody responses to a wide variety of Ag--developed arthritis though they do not bear the susceptible H-2q and H-2r haplotypes. Out of the two lines (HI and HII) selected for their high antibody responses and bearing H-2q, only one (HI) developed arthritis. Both the lines with amplified high or low antibody responses (HG and LG), and the lines differing in the levels of cell-mediated immunity (Hpha and Lpha), failed to develop arthritis. Collagen II autoantibodies were found in all the lines: the responses being high (HI and HG), low (LI, LII and LG), or intermediate (HII, Hpha and Lpha). The level of IgG2a autoantibodies, presumed to be the most pathogenic, was low in two (HI and LII) of the three arthritic lines, and was high in the unaffected HG line. These results show that this arthritis is not solely restricted to H-2q and H-2r haplotypes, and argue against a correlation between collagen autoantibody levels and disease incidence.
Inhibitory effect of anti-class II antibody on the spontaneous activation of B cells in patients with systemic lupus erythematosus. Analysis with IL-1 production and IL-1 receptor expression.
Authors: Tanaka Y , Saito K , Suzuki H , Eto S , Yamashita U 
Published: December 2022

Abstract
The mechanism of the spontaneous activation of B cells in patients with SLE was analyzed from the standpoint of the production of IL-1 from B cells and the expression of IL-1R on B cells. SLE B cells spontaneously produced IL-1-like factors which stimulated murine thymocyte proliferative responses. Their m.w. was about 17,000 and their isoelectric point was 4.8. The IL-1-like activity produced by B cells was absorbed with rabbit anti-IL-1 alpha antibody, but not with anti-IL-1 beta antibody. The differentiation of SLE B cells was enhanced by rIL-1 alpha, beta or IL-1-like factors produced by SLE B cells in a concentration-dependent manner. SLE B cells expressed large number of IL-1R detected by FITC-conjugated IL-1 alpha. By a Percoll gradient density centrifugation, IL-1-producing cells and B cells responsive to IL-1 were enriched in a higher density fraction, but were reduced in a lower density fraction. IL-1R-positive B cells were enriched in the lower density fraction, but were depleted in the higher density fraction. However, the expression of IL-1R on the lower density B cells was reduced by 2-day culture. The expression of IL-1R on the higher density B cells was increased during a 2-day culture. Anti-class II antibody inhibited the production of IL-1R on the higher density B cells. These results suggest that the cellular interaction among B precursor cells mediated by class II Ag induces the production of IL-1 and the expression of its receptors on their surface and the interaction between IL-1 and its receptors stimulates B precursor cells to spontaneously differentiate into Ig-producing cells as an autocrine mechanism in patients with SLE.
Monoclonal antibodies that bind to distinct epitopes on Fc gamma RI are able to trigger receptor function.
Authors: Guyre P M , Graziano R F , Vance B A , Morganelli P M , Fanger M W 
Published: December 2022

Abstract
The human monocyte and macrophage Fc receptor that binds human IgG with high affinity is a surface glycoprotein with a relative molecular mass of approximately 70 kDa. This receptor (Fc gamma RI) has been partially characterized using mAb 32 which binds outside the Fc binding domain of the receptor, but nonetheless triggers Fc receptor-dependent functions. In this study, we describe the properties of four new antibodies with specificity for Fc gamma RI. Based on additivity and cross-blocking studies, we conclude that two of these antibodies (mAb 22 and 44) define a third epitope which is distinct from the binding sites for both mAb 32 and the Fc portion of human IgG. Each Fc gamma RI-specific hybridoma was selected for stable sublines expressing high levels of mAb on the cell surface, and then tested for the ability of this surface mAb to trigger antibody-dependent cell cytotoxicity. All sublines were killed by human monocytes when used as targets in a 51Cr-release assay, whereas hybridomas specific for myeloid Ag other than Fc gamma RI were not killed. We conclude that Fc receptor function is triggered through binding to each of the three epitopes of Fc gamma RI that we have defined. These mAb will be useful for additional characterization of Fc gamma RI, and may, when incorporated into tumor-directed heteroantibodies, enhance tumor cell killing by human monocytes and macrophages.
Heterogeneity of protein kinase C isoenzyme gene expression in human T cell lines. Protein kinase C-beta is not required for several T cell functions.
Authors: Koretzky G A , Wahi M , Newton M E , Weiss A 
Published: December 2022

Abstract
An early consequence of stimulation of T cells via their Ag receptor is the activation of protein kinase C (PKC). It has recently been shown that PKC activity resides in a family of homologous proteins. Inasmuch as T cells are phenotypically and functionally heterogeneous, we examined the possibility that this heterogeneity may be reflected in differential expression of message for PKC isoenzyme genes. RNA from six leukemic T cell lines was probed for PKC-alpha, -beta, and -gamma message before and after activation. These studies revealed significant differences among these lines. None expressed mRNA for PKC-gamma. Whereas all cells possessed message for PKC-alpha, there was consistent variability in the level expressed. The greatest heterogeneity was seen with PKC-beta. Two cell lines, HUT 78 and HPB-ALL, did not hybridize with the beta probe under any conditions tested. We subsequently used these PKC-beta negative cells to study the role of this isoenzyme in mediating some of the effects seen with phorbol esters that directly bind to and activate PKC. Our results indicate that PKC-beta, which is expressed in some T cells, is not necessary for PMA-induced CD3 or CD4 internalization, IL-2 production, or acquisition of the p55 chain of the IL-2 receptor.
Protease-modulation of neutrophil superoxide response.
Authors: Kusner D J , King C H 
Published: December 2022

Abstract
Although prior studies with mAb have defined an endogenous chymotrypsin-like protease in the neutrophil (polymorphonuclear leukocyte (PMN)) membrane that is associated with initiation of superoxide response to inflammatory stimuli, it is not known whether extracellular proteases (in the inflammatory milieu) can also influence PMN activation. This study examined the ability of four neutral proteases: cathepsin G, elastase, chymotrypsin, and trypsin, to modify PMN superoxide response to FMLP, PMA, and arachidonate. In response to 1 microM FMLP, PMN treated with cathepsin G, chymotrypsin, or elastase showed 64%, 60%, and 32% increases, respectively, in superoxide generation when compared with control, untreated cells (p less than 0.05 for each). These increments were dependent on intact enzymatic function of the proteases, were greatest when enzyme and stimulus were added concurrently, and persisted after PMN were washed free of enzyme. Enhancement of superoxide response was not stimulus specific; in response to 10 ng/ml PMA, cells treated with cathepsin G showed a 84%, and elastase a 57%, increase in superoxide generation (p less than 0.05 for both) with a marked reduction in the time required for onset of this response. For cell activation with 80 microM arachidonate, treatment with elastase produced a 180% increase in superoxide production (p less than 0.025). Neutrophils incubated with trypsin demonstrated significant decreases in superoxide response to PMA (-34%, p less than 0.05) and arachidonate (-39%, p less than 0.01). The enzymes themselves were not stimuli for superoxide production nor were they scavengers for superoxide in cellfree system. We conclude that local release of the PMN primary-granule neutral proteases, cathepsin G, and elastase within inflammatory sites can augment neutrophil effector function by up-regulating oxidative response to defined inflammatory stimuli. This autocrine/paracrine function may provide a significant increase in antimicrobial activity, but may also enhance the potential for host tissue injury.
Interactions of Plasmodium berghei sporozoites and murine Kupffer cells in vitro.
Authors: Seguin M C , Ballou W R , Nacy C A 
Published: December 2022

Abstract
Malaria sporozoites must leave the bloodstream and cross a layer of sinusoidal lining cells in order to infect hepatocytes and undergo exoerythrocytic schizogony. To determine whether Kupffer cells (KC) derived from this layer interact with sporozoites, murine KC were isolated from perfused livers of BALB/cJ mice and incubated in vitro with Plasmodium berghei sporozoites. Isolated KC had characteristic macrophage surface Ag and were phagocytic, ingesting both latex particles and Leishmania major amastigotes. In the absence of immune serum, sporozoites associated with fewer than 10% of these KC. By 30 min, 10% of the cell-associated sporozoites were completely ingested, 30% were in the process of being ingested, and 60% were attached to the surface of the cells. Opsonization of sporozoites with monoclonal or polyclonal antibodies directed against P. berghei circumsporozoite protein markedly enhanced sporozoite association with KC. Up to 40% of cells exposed to opsonized sporozoites had parasites inside or attached to their surfaces. Sporozoites attached to or ingested by KC were uniformly destroyed within 240 min in all cultures; there was no evidence of conversion of sporozoites to the exoerythrocytic stage within KC by light microscopy, and there was no evidence of residual sporozoites, either inside or outside of cells, by either light or electron microscopy. These data suggest that under nonimmune conditions, KC play a minor role in resistance to infection by malaria sporozoites. However, when sporozoites are opsonized by circumsporozoite antibodies, phagocytosis by KC may be an important immune mechanism that prevents parasitization of hepatocytes.
Origin and fate of IgE-bearing lymphocytes. II. Modulation of IgE isotype expression on Peyer's patch cells by feeding with certain bacteria and bacterial cell wall components or by thymectomy.
Authors: Durkin H G , Chice S M , Gaetjens E , Bazin H , Tarcsay L , Dukor P 
Published: December 2022

Abstract
Mechanisms regulating the appearance of sIgE+ B lymphocytes appear to be lacking in adult germfree (GF) rats in that their Peyer's patches (PP) contain high numbers of cells with sIgE (approximately 15% of total cells), one-half of which simultaneously express sIgA, whereas sIgE+ cells are absent from PP of conventional rats (less than 1%). GF rat PP also contain elevated numbers of sIgA+ cells and decreased numbers of sIgM+ cells, with elevated numbers of sThy-1+ RT 7.1+ Ig- T cells, and reduced numbers of sThy-1- RT 7.1+ Ig- T cells. The cellular composition of PP of GF rats was converted to that resembling a conventional rat within 18 h after either 1) use of standard (unautoclaved) food; 2) feeding with certain bacteria (Clostridium difficile, Corynebacterium pseudodiphtheriticum, Mycobacterium tuberculosis, and Klebsiella pneumoniae), in either live or heat-killed, but not autoclaved form; or with certain bacterial cell wall components: murein (peptidoglycan), and its synthetic derivatives, muramyltripeptide phosphatidylethanolamine and desmethyl-muramyldipeptide, but not with LPS, core lipid A or lipoprotein; there was no effect if any bacterial cell wall component was injected i.v.; or 3) thymectomy. Each procedure resulted in elimination of sIgE+ B cells and normalization of the other surface isotypes, and loss of sThy-1+ RT 7.1+ Ig- T cells and normalization of sThy-1- RT 7.1+ Ig- T cells. Irrespective of treatment, no sIgE+ cells were detected in bone marrow, thymus, other lymphoid organs or blood, excluding the possibility that the elimination of these cells from PP was associated with their redistribution to other sites. Thus, exposure to gut flora and bacterial peptidoglycan components may have resulted in IgE isotype switching, either directly or through the mediation of accessory and/or sThy-1+ RT 7.1+ regulatory T cells. The sites in which sIgE+ B cells are down-regulated appear to be PP.
Activation of a suicide process of thymocytes through DNA fragmentation by calcium ionophores and phorbol esters.
Authors: Kizaki H , Tadakuma T , Odaka C , Muramatsu J , Ishimura Y 
Published: December 2022

Abstract
Calcium ionophore, A23187, is known to be a comitogen, but it activates a suicide process characterized by DNA fragmentation at linker regions in mouse immature thymocytes. It did not induce DNA fragmentation in T lymphocytes prepared from lymph node and spleen cells. Induction of DNA fragmentation by A23187 depends on protein phosphorylation and synthesis of mRNA and protein, because an inhibitor of protein kinase, 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine dihydrochloride (H-7), actinomycin D, and cycloheximide, respectively, inhibits the DNA fragmentation and cell death. Studies adding the inhibitors at various times show that protein phosphorylation and mRNA synthesis occur within a few hours after incubation with A23187 followed by the protein synthesis responsible for inducing DNA fragmentation. Phorbol esters, 12-O-tetradecanoyl 13-acetate (TPA) and phorbol 12,13-dibutyrate (PBD), which are capable of activating protein kinase C, also induced similar DNA fragmentation in immature thymocytes, followed by cell death. PBD committed the suicide process after 6 h of incubation, because the DNA fragmentation above the control level was not induced when PDB was removed from the medium before 6 h of incubation. A23187 or a phorbol ester alone induced DNA fragmentation followed by cell death, whereas the addition of TPA at low concentration inhibited the DNA fragmentation induced by A23187 accompanied with an increase in DNA synthesis. The result suggests that TPA switched a suicide process induced by A23187 to an opposite process: stimulation of DNA synthesis. Physiologic factors and mechanisms which regulate cell proliferation and death in the thymus are not known at present, but the signals by protein kinases and calcium ions may regulate both cell proliferation and death, independently, synergistically or antagonistically.
Two better cell lines for making hybridomas expressing specific T cell receptors.
Authors: White J , Blackman M , Bill J , Kappler J , Marrack P , Gold D P , Born W 
Published: December 2022

Abstract
Two variants of the AKR thymoma BW5147 have been isolated which can no longer express functional TCR alpha- and beta-chains. By generating hybridomas with these variant fusion lines, TCR of any normal T lymphocyte, including TCR-gamma/delta, can be studied at a clonal level, without interference of the BW5147-derived receptor chains. In this study one of the variants has been useful in identifying the reactivity to allogeneic MHC Ag of BW5147 itself.
Inhibition of erythroid progenitor growth is mediated by cytotoxic lymphocytes and not by natural killer cells or IFN-gamma.
Authors: Torok-Storb B , Graf L , Shankar P 
Published: December 2022

Abstract
Alloantigen primed T cells (PTC) were recovered from MLR at day 6 and 12, then added to cultures of erythroid progenitors, erythroid burst-forming units, BFU-E. The PBMC source of BFU-E was prepared either to retain or deplete APC by treatment with appropriate mAb and C. BFU-E grown in cocultures were counted at day 14 and replicate cultures assayed for IFN-gamma production on days 1 to 7. Analysis of MLR cells indicated that large, rapidly cycling cells recovered from MLR at day 6 have significant NK activity, whereas CTL activity is minimal, and production of IFN-gamma requires reexposure to APC. The smaller, noncycling cells recovered from MLR at day 12 have comparable NK activity, also require reexposure to APC for IFN-gamma production, but in addition have significant CTL activity. The addition of day 12 MLR cells to BFU-E cultures results in MHC restricted inhibition of BFU-E growth, suggesting that the CTL activity and not the NK activity contained within this population of cells is responsible for BFU-E inhibition. Studies using enriched population of BFU-E indicated that appropriate APC are needed to trigger both IFN-gamma production and BFU-E inhibition by the PTC. By using various APC-BFU-E combinations it was determined that after reexposure of PTC to appropriate APC, the inhibition of BFU-E was still target-specific indicating a direct effect between the PTC and BFU-E.