bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressive effect of T cell proliferation via the CD29 molecule. The CD29 mAb 1 "K20" decreases diacylglycerol and phosphatidic acid levels in activated T cells.
Authors: Ticchioni M , Aussel C , Breittmayer J P , Manié S , Pelassy C , Bernard A 
Published: December 2022

Abstract
We had previously reported that the CD29 mAb "K20," presented in a soluble form, blocks peripheral T cell proliferation/activation induced by a CD3 mAb. To better characterize the negative signal delivered by soluble K20, we have investigated its effects on the phospholipid metabolism, both in Jurkat and CD4+ T cells. In CD3-activated T cells, K20 inhibited the increase of diacylglycerol (DAG) and phosphatidic acid levels, but did not modify phosphatidylinositol 4,5-bisphosphate levels, cytosolic Ca2+ raise, and inositolphosphates formation, indicating that K20 did not inhibit phosphatidylinositol 4,5-bisphosphate hydrolysis by phospholipase C-gamma. Moreover, in these conditions, K20 increased phosphatidylethanolamine levels, without variation of phosphatidylcholine, phosphatidylserine, and phosphatidylinositol, suggesting that K20 specifically increased the phosphatidylethanolamine biosynthesis from DAG. Thus, the effects of K20 on DAG and phosphatidic acid levels resulted from an accelerated catabolism rather than from a defect of synthesis. That K20 acts solely at an early step of T cell activation, namely before the binding of IL-2 to its receptor, is supported by the observation that adding exogenous rIL-2 increased proliferation in spite of K20. These results suggest that the beta 1 integrin molecules interact with the membrane phospholipid metabolism and they appear to be the hallmark of a peculiar negative pathway of T cell activation, likely to play an important regulatory role mediated via the T cell integrin molecules.
In vivo dimeric association of class I MHC heavy chains. Possible relationship to class I MHC heavy chain-beta 2-microglobulin dissociation.
Authors: Capps G G , Robinson B E , Lewis K D , Zúñiga M C 
Published: December 2022

Abstract
Class I MHC molecules have been thought to occur in vivo both as class I MHC heavy chain-beta 2-m heterodimers, which are or are not associated with antigenic peptide, and as free class I MHC heavy chains. Class I MHC molecules are now found also to occur in another type of structure: a heavy chain-heavy chain dimer. Biochemical studies show that heavy chain dimers are disulfide-linked via a conserved cytoplasmic domain cysteine. H-2Ld, H-2Db, and H-2Dd class I dimers fail to react with certain alpha 1 and alpha 2 domain-specific antibodies. Furthermore, although beta 2-m-specific antibodies coprecipitate class I MHC heavy chains, they do not coprecipitate class I MHC heavy chain dimers. Pulse-chase studies show that heavy chain dimer formation occurs at different points in the biosynthesis of class I MHC molecules in beta 2-m+ and beta 2-m- cells: in beta 2-m+ cells, heavy chain dimers form after the class I molecules have traversed the medial Golgi cisternae, whereas in beta 2-m- cells they form immediately. Culturing of beta 2-m+ cells with exogenous beta 2-m prevents the formation of H-2Ld/Db heavy chain dimers. We conclude that dimer formation occurs as a consequence of loss or unavailability of beta 2-m. Class I MHC heavy chain dimerization may provide a mechanism for removal of immunologically dysfunctional molecules.
Differential amino-terminal anchors for peptide binding to H-2M3a or H-2Kb and H-2Db.
Authors: Shawar S M , Vyas J M , Shen E , Rodgers J R , Rich R R 
Published: December 2022

Abstract
We previously established that H-2M3a, the H chain of the maternally transmitted Ag (Mta), is specialized for presentation of N-formylated peptides. We hypothesized that the N-formyl group might prevent or limit the presentation of peptide Ag by H-2K and H-2D molecules. We now show by Mta- and OVA-specific CTL assays, peptide competition, and immunofluorescence analyses that N-formyl modification of four antigenic peptides inhibited their binding by either H-2Kb (OVAMet258-264, VSVNP52-59, and SVNP324-332) or H2-Db (SVNP324-332, and IVNP366-374). In contrast, N-formyl-OVAMet258-264 did bind to H2-M3a. The data imply lack of an N-formyl-binding pocket in classical MHC class I molecules and are consistent with a specialized role for H2-M3a in presentation of N-formylated peptides such as derived from intracellular prokaryotic parasites.
Candidate vaccine antigens that stimulate the cellular immune response of mice vaccinated with irradiated cercariae of Schistosoma mansoni.
Authors: Richter D , Reynolds S R , Harn D A 
Published: December 2022

Abstract
Vaccination with radiation-attenuated cercariae confers the highest levels of resistance to challenge infection in experimental schistosomiasis and requires Ag-specific T cells. Therefore, this study aimed to identify specific Ag that stimulate the cellular immune response of mice vaccinated with irradiated cercariae of Schistosoma mansoni. Four experimental groups representing different levels of resistance in the vaccine model (C57BL/6J versus CBA/J mice vaccinated with 15- or 50-krad irradiated cercariae) were compared for in vitro lymphocyte proliferation and lymphokine production. Adult worm extracts fractionated by isoelectric focusing were used as Ag. Lymphocyte proliferation of all groups was limited to three consecutive isoelectric fractions (pH 4.6-6.3). Interestingly, the antibody response of these mice was directed to Ag in the same isoelectric fractions, three of which had previously been identified as paramyosin, heat shock protein 70, and the integral membrane protein Sm23. These Ag as well as two 28 kDa proteins, triosephosphate isomerase and glutathione S-transferase, in purified native or recombinant form or as a synthetic peptide, stimulated lymphocyte proliferation. Lymphocytes of vaccinated C57BL/6J mice generally showed higher levels of proliferation than did CBA/J mice. Interestingly, cells of once-vaccinated mice responded better than did cells of mice vaccinated three times. Lymphokine assays demonstrated that IL-2 and IL-4 was generally reduced after multiple vaccinations and varied qualitatively as well as quantitatively between mouse strains. This study substantiates that the five Ag, paramyosin, heat shock protein 70, triosephosphate isomerase, glutathione S-transferase, and the integral membrane protein Sm23, are important candidates for a defined antischistosomal vaccine.
Signaling properties of CR3 (CD11b/CD18) and CR1 (CD35) in relation to phagocytosis of complement-opsonized particles.
Authors: Fällman M , Andersson R , Andersson T 
Published: December 2022

Abstract
Human neutrophils preincubated with antibodies against complement receptor type 1 (CR1) (anti-CD35) and/or complement receptor type 3 (CR3) (anti-CD11b or anti-CD18) exhibited a reduced ability to engulf complement-opsonized yeast particles, whereas cellular adhesion of these particles was reduced only in the presence of anti-CD35 antibodies. These data support the idea that CR1 primarily promotes the adhesion of particles and CR3 mediates the subsequent engulfment. However, the effects of anti-CR1 and anti-CR3 antibodies on particle-induced diglyceride production correlate with the effects of these antibodies on the cellular uptake of the particles. Hence, it seems reasonable to suggest that CR1 also participates in mediating the signal(s) that induce particle uptake. This idea is further supported by the findings that cross-linking surface-bound anti-CD11b, anti-CD18 as well as anti-CD35 antibodies results in activation of phospholipase D (PLD), a signal closely associated with phagocytosis of complement-opsonized yeast particles in human neutrophils. The signaling property of CR1 was further revealed by the observation that cross-linking of surface-bound anti-CD35 triggered a rapid and transient mobilization of intracellular Ca2+, a signal most likely involved in the phagosome-lysosome fusion that occurs after the uptake of a particle. Pretreatment with PMA, which positively modulates CR-mediated engulfment of particles, was found to potentiate the CR3- and CR1-induced activation of PLD but impair the activation of phospholipase C, giving added support to the idea that PLD activation is the principal signal for the engulfment process. The activation of PLD was also increased by stimulating the cells with anti-CD18 or anti-CD35 antibodies prefixed on Staphylococcus aureus particles, instead of cross-linking cellular-bound antibodies, suggesting that the form of ligand presentation is a critical parameter of phagocytic signaling. Taken together, the present results demonstrate that both CR1 and CR3 can initiate transmembrane signaling in human neutrophils and, in particular, activation of PLD. This activation was also further recognized as an important signal regulating the engulfment of complement-opsonized particles.
Improved renal function in mouse kidney allografts lacking MHC class I antigens.
Authors: Coffman T , Geier S , Ibrahim S , Griffiths R , Spurney R , Smithies O , Koller B , Sanfilippo F 
Published: December 2022

Abstract
The immunological responses that lead to rejection of organ and tissue transplants are triggered by the recognition of proteins encoded within the MHC. The relative contributions of responses directed toward MHC class I compared with class II in the loss of functional integrity of vascularized organ grafts have been difficult to define. The recent development of technologies which allow the generation of mice in which specific genes have been altered by gene targeting offers a new approach to addressing this question. We examine here the rejection of kidney allografts from mice lacking native MHC class I Ag. These mice were obtained from embryonic stem cells in which the beta 2 microglobulin (beta 2m) gene had been disrupted by homologous recombination. We found a significant improvement in function of renal allografts from MHC class I-deficient donors compared with allografts from donors with normal MHC class I expression. Surprisingly, the improved function of the MHC class I-deficient grafts was not associated with differences in mononuclear inflammatory cell infiltration of these grafts nor in differences in alloreactive proliferative or cytotoxic T cell responses. However, we did find differences in alloantibody response between the groups. Recipients of control allografts produced antibodies against both donor MHC class I and II, whereas recipients of MHC class I-deficient grafts formed alloantibodies primarily against donor MHC class II Ag. These studies confirm that immune responses directed toward donor MHC class I alloantigens contribute to kidney transplant dysfunction in this model. Also, these findings suggest that, at least for renal transplants, genetic manipulations which reduce MHC class I expression may be effective in overcoming some of the effects of MHC incompatibility.
Phosphorylation of CD20 in cells from a hairy cell leukemia cell line. Evidence for involvement of calcium/calmodulin-dependent protein kinase II.
Authors: Genot E M , Meier K E , Licciardi K A , Ahn N G , Uittenbogaart C H , Wietzerbin J , Clark E A , Valentine M A 
Published: December 2022

Abstract
Hairy cell leukemia is an uncommon B cell lymphoproliferative disease of unknown etiology. We previously observed that CD20, a membrane protein involved in B cell activation, is hyperphosphorylated on hairy cells and that these cells have unusually high levels of intracellular free Ca2+. Therefore, we used a hairy cell line, HCLL-7876, to study the potential involvement of Ca(2+)-activated protein kinases in CD20 phosphorylation. Addition of the Ca2+ ionophore, ionomycin, increased CD20 phosphorylation both in activated B cells and in cells from the hairy cell line; addition of EGTA to either cell type decreased basal levels of CD20 phosphorylation. Ionomycin treatment of these cells resulted in increased kinase activity of cytosolic extracts toward syntide-2, a synthetic peptide substrate for calcium/calmodulin-dependent kinase II (CaM-KII), with kinetics similar to those of CD20 phosphorylation in the cell line. CD20 isolated from the cell line was a substrate for purified CaM-KII in vitro. Phosphopeptide maps of CD20 from untreated hairy cells or ionomycin-treated HCLL-7876 cells were similar to maps of CD20 that had been phosphorylated in vitro by CaM-KII. These results suggest that the unusually high levels of intracytoplasmic Ca2+ in hairy cells may enhance the phosphorylation of key surface proteins.
Construction of recombinant human type 5 adenoviruses expressing rodent IL-6 genes. An approach to investigate in vivo cytokine function.
Authors: Braciak T A , Mittal S K , Graham F L , Richards C D , Gauldie J 
Published: December 2022

Abstract
The majority of biologic functions assigned to cytokines have been characterized by in vitro assay systems which may not necessarily reflect cytokine roles in vivo. Recently, recombinant virus approaches have allowed tissue-specific expression of foreign gene products in experimental animal models. We have constructed recombinant human type 5 adenoviruses, deficient in the E3 region of the genome, with incorporated rodent IL-6 cDNA that express significant levels of biologically active IL-6 on infection both in vitro and in vivo. After i.p. injection, the liver, spleen, and peritoneum appear to be primary sites of expression, whereas the lung and bronchus are the main sites of expression after intratracheal instillation. Injection i.p. of BALB/c mice with the murine rIL-6 virus causes an increase in serum levels of bioactive IL-6 for up to 6 days post-infection, whereas similar changes are not seen in animals infected with control viruses. Coincident with enhanced plasma levels of IL-6, we detect raised serum levels of hepatic-derived acute phase proteins. Associated with the expression of IL-6 in the liver and spleen, at 7 days we note a fourfold splenomegaly with expansion of B and T cell compartments, as well as the presence of lymphoid aggregates in the liver. These morphologic changes had resolved by 16 days. Our findings demonstrate that recombinant human type 5 adenoviruses expressing cDNA for various cytokines could be used as a transient pseudo-transgenic animal model to investigate the biologic function of cytokines in vivo.
cAMP analogs prevent activation-induced apoptosis of T cell hybridomas.
Authors: Lee M R , Liou M L , Liou M L , Yang Y F , Lai M Z 
Published: December 2022

Abstract
Activation of T cell hybridomas through their TCR leads to secretion of IL-2, inhibition of proliferation, and apoptosis. The identification of various inhibitors that prevent activation-induced T cell death (AICD) has helped identify several essential events in apoptosis. For example, inhibition of AICD by dexamethasone indicates a connection between these two programmed death pathways. In this study, we have investigated the interaction between the cAMP signal transduction pathway and the activation- or glucocorticoid-induced cell death. cAMP induced DNA fragmentation in thymocytes. T cell hybridomas displayed different sensitivity to cAMP. Regardless of its cAMP sensitivity, programmed cell death promoted by anti-CD3 or Ag in hybridoma was prevented by the presence of cAMP analogs. In contrast, cAMP had no effect on glucocorticoid-induced T cell death. The inhibitory effect of cAMP on AICD was unlikely to be due to quenching of T cell activation signals, because cAMP added 1 h after T cell activation could still prevent cell death. In addition, the increased binding of AP-1, NF-AT, and NF-kappa B during T cell activation was not significantly affected by cAMP. The presence of the inhibitory cAMP-mediated signals, together with the glucocorticoid-induced pathway, suggest there are at least two distinct mechanisms regulating AICD in immature lymphocytes.
Lymphocytes infiltrating rat cardiac allografts express a limited repertoire of T cell receptor V beta genes.
Authors: Shirwan H , Chi D , Makowka L , Cramer D V 
Published: December 2022

Abstract
The T cell response to many self-MHC-restricted nominal Ag involves limited use of the TCR repertoire. The status of the TCR repertoire in allogeneic responses remains unclear. In this report, we have studied the TCR V beta gene repertoire involved in the rejection of cardiac allografts disparate for major and minor histocompatibility Ag in rats. Graft-infiltrating lymphocytes (GIL) were isolated from rejecting heart allografts and analyzed for the expression of the V beta repertoire using a cDNA library and a semiquantitative polymerase chain reaction (PCR). We report here that GIL isolated at early stages of the rejection reaction preferentially use the V beta 4 gene. First, V beta 4 comprised 36.4% (8/22) of randomly sequenced cDNA clones isolated from a TCR-beta chain-specific cDNA library established from GIL harvested 3 days posttransplantation. The V beta 4 gene in these clones was found in conjunction with several different J beta and N regions, suggesting a dominant role for the V beta 4 encoded domains in the recognition of allograft Ag. Second, the V beta 4 message comprised 56.6 to 65.7% of the transcripts expressed by the 20 rat V beta genes in three T cell lines established from GIL isolated 2 days posttransplantation. Third, fresh, unmanipulated GIL harvested at days 2 and 3 posttransplantation predominantly expressed the V beta 4 gene. Fourth, the expression of V beta 4 in naive splenocytes constituted only 5.4% of the V beta detected, suggesting that the predominant use of the V beta 4 gene by GIL was not a consequence of its high level of expression in the periphery. The limited use of the TCR repertoire in allograft rejection may provide the opportunity to interrupt the rejection process and induce donor-specific tolerance by targeting a select population of T cells for inactivation or elimination.
Natural killer cells induce activated murine B cells to secrete Ig.
Authors: Snapper C M , Yamaguchi H , Moorman M A , Sneed R , Smoot D , Mond J J 
Published: December 2022

Abstract
We previously demonstrated that dextran-conjugated anti-IgD antibodies (alpha delta-dex) induce proliferation of small, B cell-enriched murine spleen cells (Be cells), and in the presence of IL-2, stimulate Ig secretion in vitro. We have shown that alpha delta-dex-stimulated B cells provide an in vitro model for studying B cell activation by T cell-independent type 2 (TI-2) Ag, as exemplified by the bacterial polysaccharides. We now show that highly purified resting B cells, obtained by electronic cell sorting (Bsp cells), fail to secrete Ig in the presence of alpha delta-dex + IL-2. The alpha delta-dex + IL-2-induced Ig secretory response of Bsp cells is restored upon addition of splenic non-B, non-T cells or a pure population of in vitro-generated NK cells. Similarly, pretreatment of Be cells with anti-AsGm-1 plus complement inhibits Ig secretion in response to alpha delta-dex + IL-2. An IL-2-induced NK cell supernatant (NKSN) is equally potent at stimulating Ig secretion by alpha delta-dex-activated Bsp cells, indicating that cell contact between Bsp and activated NK cells is not required for this effect. IL-2 stimulates not only NK cells, but B cells as well, since addition of anti-IL-2 + anti-IL-2R antibodies to Bsp cell cultures, in the presence of alpha delta-dex + NKSN, inhibits Ig secretion. These data describe a novel animal model for NK cell-induced B cell maturation to Ig secretion and suggest a pathway for Ig production in response to T1-2 Ag.
Recruiting memory B cells with changed antigenic specificity.
Authors: Ellenberger J , Creadon G , Zhang X , Wysocki L J 
Published: December 2022

Abstract
During T cell-dependent antibody responses, the V region genes of responding B lymphocytes are physiologically mutated at a high rate. An intense selection process expands subclones of B cells producing mutant antibodies that bind Ag optimally. This implies that most mutant B cells and their antibody products are unselected and not often observed by conventional hybridoma or serum sampling procedures. Herein we show that the pool of mutant B cells includes unselected members that have acquired new antigenic specificities. Mice were immunized with a haptenated carrier protein to recruit and somatically diversity hapten-specific B cells producing antibodies with a defined V region bearing a major idiotype. During the primary immune response, the mice were given booster injections with a second related hapten conjugated to the same carrier. Hybridomas were isolated that produced idiotypic antibodies binding the second hapten but not the first. V gene sequencing analyses conclusively demonstrated that one of these was derived from a precursor B cell that expressed the defined unmutated V region with specificity for the first hapten. Sequence of the V genes expressed by the remaining six hybridomas supported this interpretation. In essence, single B cell clones were mutationally diversified to include members that had lost an original antigenic specificity while acquiring a new one, and the mutants were recruited into the memory compartment by antigenic selection. These results support the view that selection processes in vivo normally reveals only a small fraction of a mutationally diversified B cell clone. They also suggest a potential route by which antibodies of differing antigenic specificities can be generated from a single B cell clone of predefined origin and antigenic specificity.
Length and sequence requirements of the cytoplasmic domain of the A beta molecule for class II-mediated B cell signaling.
Authors: Harton J A , Bishop G A 
Published: December 2022

Abstract
APC use class II molecules of the MHC to present peptide Ag to Th cells. Interaction of the TCR and CD4 with the class II-peptide complex, together with co-stimulatory signals provided by the APC, activates the T cell. B lymphocytes express class II molecules and can also be induced to express co-stimulatory molecules, allowing them to act as APC to Th cells. In addition to T cell activation, class II binding by T cells has been shown to result in the transmission of signals to B cells. Signal transduction via MHC class II has been well documented in B cells of both mice and humans and is implicated in the processes of cellular adhesion, Ag presentation, and Ag-dependent B cell activation. The regions of the class II MHC molecule which are involved in signal transduction to the B cell are not clearly defined. However, previous studies have suggested that the beta chain of the alpha beta heterodimer has a predominant role in B cell signaling. To examine the role of the cytoplasmic domain of this molecule in class II-mediated signaling to a mouse B cell clone, we have prepared and analyzed a set of subclones expressing sequentially truncated forms of A beta b. Our results demonstrate that only the 8 membrane-proximal amino acids of the cytoplasmic domain are required for signaling. However, specific conserved amino acids within this minimal length are required for successful signal transduction; length alone is not sufficient. Examination of the signaling ability of these truncated beta chains suggests that conserved residues at positions 227 and 228 of the cytoplasmic domain may have particularly important effects on signal transduction. A beta b chains from which the entire cytoplasmic domain have been removed are still capable of transmitting a detectable, although reduced, signal to B cells. Thus, the transmembrane and/or extracellular domains may also be involved in the signaling process.