bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coding sequence polymorphisms among V beta T cell receptor genes.
Authors: Smith L R , Plaza A , Singer P A , Theofilopoulos A N 
Published: December 2022

Abstract
The four V beta gene segments, V beta 1, 3.1, 6, and 10, which previously have been shown by RFLP analyses to differ between TCR V beta a and V beta b haplotypes, were cloned and sequenced from V beta a SWR mice and compared with V beta b strains to define coding sequence polymorphisms distinguishing these haplotypes. V beta 3.1 and 6 alleles differed between strains by a single amino acid, whereas V beta 1 and 10 alleles differed by 4 and 6 amino acids, respectively. The overall interhaplotypic V beta polymorphisms appeared to be limited when based upon compilation of this information and previously published V beta sequences. One application of these data was to attempt to elucidate the molecular basis underlying the recently reported allele-specific autoimmune disease, collagen-induced arthritis. Based on the present structural data and the additional evidence, contrary to what was suggested, the V beta 6 gene does not appear to be the sole participant in anticollagen responses.
Generation and characterization of hamster-mouse hybridomas secreting monoclonal antibodies with specificity for lipopolysaccharide receptor.
Authors: Bright S W , Chen T Y , Flebbe L M , Lei M G , Morrison D C 
Published: December 2022

Abstract
Experiments are described for the partial purification of the 80-kDa LPS binding protein expressed on macrophages and lymphocytes. This partially purified Ag was used to immunize adult Armenian hamsters and splenocytes from immunized animals were fused with murine myeloma cell lines. Hybridoma cell culture supernatants containing mAb were screened by ELISA for positive binding to the immunizing Ag, murine splenocytes and the murine 70Z/3 pre B cell and for an absence of binding to sheep E. Positive clones were further screened for reciprocal competitive binding with LPS on spleen cells and ability to modulate B lymphocyte mitogenic activity. Two hybridoma cell lines secreting IgM monoclonals, termed mAb3D7 and mAb5D3, were identified that satisfied all of the selection criteria. These hybridoma cell lines were subcloned and expanded. Binding of one (mAb3D7) was abrogated by treatment of Ag with mild periodate; binding of the second (mAb5D3) was destroyed by digestion of Ag with proteinase K. Binding specificity for mAb5D3 has been confirmed by ELISA using highly purified 80-kDa protein. These mAb have been of value in establishing that the 80-kDa LPS binding protein previously identified may serve as a specific functional receptor for LPS.
Dual molecular mechanisms mediate ligand-induced membrane Ig desensitization.
Authors: Cambier J C , Fisher C L , Pickles H , Morrison D C 
Published: December 2022

Abstract
We have previously shown that ligation of murine B cell membrane IgM or IgD can lead to inactivation of the signal transducing ability of unligated Ag receptors. We describe further studies of the molecular basis of this desensitization. Consistent with the possibility that ligand induced desensitization is mediated by protein kinase C (PKC) are findings that demonstrate that both Ig binding ligands and PKC activators (DIC8 or PMA) induce desensitization in virtually all resting B cells. However, ligand-induced desensitization is longer lived than PMA- or DIC8-induced desensitization and insensitive to the PKC inhibitor staurosporine. Further, biochemical studies indicate that insufficient PKC activation is induced by ligation of membrane Ig to mediate the observed desensitization. Thus data indicate that PKC must play only a minor role in ligand-induced membrane Ig desensitization. Further studies explored the molecular source and target of effectors that mediate ligand-induced desensitization. Data indicate that phosphoinositide hydrolysis is neither necessary nor sufficient for ligand induction of desensitization. Finally, ligand-induced desensitization appears to be mediated by uncoupling of membrane Ig from G proteins that regulate phospholipase C because ligand desensitized cells are hyperresponsive to agents including ALF4- and mastoparan which activate G proteins leading to mobilization of Ca2+. Thus, the function of G proteins and further downstream elements that mediate Ca2+ mobilization is intact. Taken together, these data are most consistent with ligand-induced membrane Ig desensitization being mediated by a non-PKC, non phosphatidylinositol 4,5-bisphosphate hydrolysis involving mechanism that has as its target a structure that is very proximal to the receptor, such as the receptor itself or a transducer complex analogous to CD3.
Human T lymphocyte adhesion to endothelial cells and transendothelial migration. Alteration of receptor use relates to the activation status of both the T cell and the endothelial cell.
Authors: Oppenheimer-Marks N , Davis L S , Lipsky P E 
Published: December 2022

Abstract
An in vitro model of T cell adhesion to human umbilical vein endothelial cells (HUVEC) and transendothelial migration was used to determine whether the activation state of the T cell or cytokine exposure of the HUVEC altered T cell-HUVEC interactions or receptor utilization. Stimulation of T cells with the activator of protein kinase C, phorbol dibutyrate (PDB) alone or in combination with the calcium ionophore, ionomycin increased their binding to HUVEC. Much of the binding of control and activated T cells to HUVEC was mediated by leukocyte function-associated Ag-1 (LFA-1) (CD11a/CD18), because mAb to either chain of this molecule inhibited binding substantially, but not completely. Activation of HUVEC with IL-1 also increased binding of T cells. Binding of control T cells to IL-1-stimulated HUVEC, however, was found to be LFA-1 independent, because mAb to CD11a/CD18 failed to block the interaction. In contrast, binding of activated T cells to IL-1-stimulated HUVEC was partially inhibited by mAb to LFA-1. Binding of activated T cells to IL-1-stimulated HUVEC also involved CD44 because this interaction was partially blocked by mAb to this determinant. When T cell migration was analyzed, it was found that the migration of PDB-activated T cells was three to four-fold more than that of control T cells. Migration through HUVEC and random migration were both enhanced by PDB stimulation. However, when the T cells were costimulated with PDB and ionomycin, migration was not increased above that of control T cells. PDB-activated T cells appeared to use LFA-1 for migration regardless of the activation status of the HUVEC, because mAb to CD11a/CD18 partially blocked their migration after binding to HUVEC. There was also a modest inhibition of PDB-activated T cell migration by mAb to CD44. In contrast, migration of control T cells involved neither LFA-1 nor CD44. Finally, binding of control T cells to high endothelial venules of peripheral lymphoid tissue was found to be CD11a/CD18 and CD44 independent, and completely inhibited by activation with either PDB or the combination of PDB and ionomycin. These results demonstrate that T cells use LFA-1 and CD44 as well as other as yet unidentified adhesion receptors for interactions with HUVEC, and that use of these adhesion receptors is mutable and related to the activation state of the T cell and cytokine stimulation of the HUVEC.
Regulation of the steady state level of Fc gamma RI mRNA by IFN-gamma and dexamethasone in human monocytes, neutrophils, and U-937 cells.
Authors: Pan L Y , Mendel D B , Zurlo J , Guyre P M 
Published: December 2022

Abstract
The high affinity IgG FcR Fc gamma RI, CD64, plays important roles in the immune response. Fc gamma RI is predominantly expressed on monocytes and macrophages, and barely detectable on neutrophils. rIFN-gamma markedly increases the expression of Fc gamma RI on neutrophils, monocytes, macrophages and myeloid cell lines such as U-937, HL-60, and THP-1. Glucocorticoids inhibit the augmentation of Fc gamma RI expression by rIFN-gamma on neutrophils and myeloid cell lines, but enhance the augmentation of Fc gamma RI expression by rIFN-gamma on monocytes. In this study, we examined the effect of rIFN-gamma and dexamethasone (Dex) on the steady state level of Fc gamma RI mRNA in U-937 cells, neutrophils, and monocytes by hybridizing total RNA with the Fc gamma RI cDNA probe, p135. We found that the amount of Fc gamma RI mRNA increased within 1 h of treatment with rIFN-gamma in all three cell types. This initial induction of Fc gamma RI mRNA by rIFN-gamma was completely blocked by an inhibitor of RNA synthesis, actinomycin D, suggesting that the rIFN-gamma-mediated induction of Fc gamma RI mRNA is dependent on gene transcription. Dex, used in combination with rIFN-gamma, partially blocked the induction of Fc gamma RI mRNA by rIFN-gamma in U-937 cells and neutrophils, but caused a synergistic increase in Fc gamma RI mRNA levels in monocytes. The inhibitory effect of Dex on the steady state level of Fc gamma RI mRNA in U-937 cells was blocked by an inhibitor of protein synthesis, cycloheximide, suggesting that Dex-induced proteins were involved in the regulation of Fc gamma RI expression. This study indicates that the regulation of Fc gamma RI expression on U-937 cells, neutrophils, and monocytes by rIFN-gamma and Dex occurs, at least in part, at the mRNA level. rIFN-gamma increases the steady state level of Fc gamma RI mRNA through a common pathway among U-937 cells, neutrophils, and monocytes, whereas the effect of Dex on rIFN-gamma-induced Fc gamma RI mRNA is cell-type specific.
Multiple calcium-mediated mechanisms regulate c-myc expression in HL-60 cells.
Authors: Salehi Z , Niedel J E 
Published: December 2022

Abstract
Treatment of human promyelocytic leukemia cells (HL-60) with the calcium ionophore A23187 induced a biphasic change in the expression of the c-myc protooncogene. Within 1 h of exposure to a single 2.5-microM dose of A23187, steady state levels of c-myc mRNA increased to 170% of control. After this early increase, c-myc mRNA expression underwent an abrupt decline over the next 2 to 4 h. Between 6 to 18 h of treatment with A23107, steady state levels of c-myc mRNA fell gradually toward zero. The early increase in expression of c-myc mRNA was mediated by both enhanced initiation of c-myc transcription and posttranscriptional stabilization of c-myc mRNA. Stimulation of HL-60 cells with A23187 for 30 min increased transcription of both exons 1 and 3 of c-myc by 125%. After 1 h of treatment with A23187, the half-life of c-myc mRNA increased to 150% of control. The late decrease in c-myc expression induced by A23187 was primarily mediated by interruption of elongation of c-myc nascent mRNA beyond exon 1. The combination of calcium ionophore A23187 and phorbol 12,13-dibutyrate acted synergistically to inhibit expression of c-myc mRNA.
Clonal deletion of self-reactive T cells at the early stage of T cell development in thymus of radiation bone marrow chimeras.
Authors: Matsuzaki G , Yoshikai Y , Ogimoto M , Kishihara K , Nomoto K 
Published: December 2022

Abstract
Sequential appearance of T cell subpopulations occurs in the thymocytes of irradiated C3H/He mice (H-2k, Mls-1b2a, Thy-1.2) after transplantation with bone marrow cells of AKR/J mice (H-2k, Mls-1a2b, Thy-1.1) (AKR----C3H chimeras). The donor-derived thymocytes of AKR----C3H chimeras on day 14 after bone marrow transplantation (BMT) contained a large number of blastlike CD4+CD8+ cells which represent relatively immature thymocytes, whereas those on day 21 after BMT consisted of small sized CD4+,CD8+ cells which represent a great part in normal thymocytes. To define the developmental stage at which clonal deletion of self-reactive T cells occurs in adult thymus, we followed the fate of V beta 6- or V beta 11-bearing T cells in the donor-derived thymocytes at the early stage of AKR----C3H chimeras. Mature thymocytes expressing high intensity of V beta 6 or V beta 11, which are involved in recognition of Mls-1a or MHC I-E gene products, respectively, were deleted from the donor-derived thymocytes on day 21. Immature thymocytes expressing low intensity of V beta 6 in CD3low thymocyte fraction decreased in proportion, whereas those expressing low intensity of V beta 11 rather increased in proportion in the donor-derived thymocytes of AKR----C3H chimeras from day 14 to day 21 after BMT. These results suggest that the clonal deletion of V beta 6-positive cells occurs just at the stage of immature CD3lowCD4+CD8+ cells, whereas the clonal deletion of V beta 11-positive cells may begin at the transitional stage from CD3lowCD4+CD8+ cells to CD3high single positive cells. Timing of negative selection of thymocytes may vary in distinct T cells capable of recognizing different self-Ag.
Concomitant administration of hapten and IL-2-toxin (DAB486-IL-2) results in specific deletion of antigen-activated T cell clones.
Authors: Bastos M G , Pankewycz O , Rubin-Kelley V E , Murphy J R , Strom T B 
Published: December 2022

Abstract
During the proliferative burst after Ag recognition, T cells express cell-surface, high-affinity IL-2R. The importance of IL-2R+ T cells in supporting/mediating tissue injury has been documented by the ability of mAb anti-IL2R therapies to prevent allograft rejection and autoimmunity. The delayed-type hypersensitivity (DTH) response, an experimental model of T-dependent immunity, offers the possibility of studying responses mounted against defined Ag. We previously reported that the chimeric IL-2 toxin (DAB486-IL-2) prevents DTH responses and selectively eliminates activated IL-2R bearing CD4 and CD8 T cells from lymph nodes draining the site of inflammation. We have examined the duration of immunosuppression and relative specificity of action of DAB486-IL-2 and anti-CD3 mAb for Ag-activated clones in a murine model of DTH using two different noncross-reacting haptens. Treatment with DAB486-IL-2 generates a state of selective unresponsiveness to subsequent challenge with the hapten introduced during the therapeutic period. Immediately after cessation of DAB486-IL-2 therapy, immunization with an unrelated hapten induces a normal vigorous immune response. By comparison, anti-CD3 mAb treatment causes a broad immunosuppression because unrelated haptens introduced after anti-CD3 therapy do not evoke a vigorous immune response. After cessation of DAB486-IL-2 toxin treatment response to the hapten is eventually restored probably by cells trafficking from the thymus, because thymectomized hosts remain unresponsive to the hapten. Taken together these data reinforce the role of the IL-2R as an important target for immunosuppression in T cell-mediated immune reactions. DAB-486-IL-2 treatment confers highly selective immunosuppression.
Presentation of Listeria monocytogenes to CD8+ T cells requires secretion of hemolysin and intracellular bacterial growth.
Authors: Brunt L M , Portnoy D A , Unanue E R 
Published: December 2022

Abstract
Cell-mediated immunity to Listeria monocytogenes (LM) involves both CD4+ and CD8+ T cell responses. An important virulence factor in the pathogenesis of infection and development of protective immunity to LM is secretion of the sulfhydryl-activated hemolysin (Hly), listeriolysin. Listeria secretion of Hly allows LM to escape the endosomal compartment and enter the cytosol of the cell where intracellular growth can occur. We developed a system using bone marrow macrophages cultured in CSF-1 or IFN-gamma for comparing the response of CD4+ or CD8+ T cells to heat-killed, live Hly-, and live Hly+ LM. Macrophages grown in CSF were permissive for intracellular growth of Hly+ but not Hly- LM. CD8+ T cells recognized Hly+ LM but not HK or Hly- LM pulsed macrophages. However, CD4+ T cells recognized all three Listeria preparations fed to IFN-gamma-treated macrophages. These results suggest that both heat-killed LM and live LM efficiently enter the exogenous pathway for class II Ag processing and presentation. In contrast, only Hly+ LM activates the class I pathway, probably as a result of Hly+ bacterial replication within the cytosolic compartment.
Rapid stimulation of large specific antibody responses with conjugates of antigen and anti-IgD antibody.
Authors: Lees A , Morris S C , Thyphronitis G , Holmes J M , Inman J K , Finkelman F D 
Published: December 2022

Abstract
Injection of mice with goat anti-mouse IgD antibody stimulates a large IgG1 anti-goat IgG antibody response, as well as polyclonal IgG1 production. To determine if this phenomenon could be used to induce large antibody responses to other Ag, covalent conjugates were produced between BSA or other Ag and H delta a/1, a mAb specific for IgD of the a allotype, and between BSA and AF3.33, a mAb specific for IgD of the b allotype. Injection of H delta a/1-BSA into BALB/c mice, which express Ig of the a allotype, or into (BALB/c x CB20)F1 mice (a x b allotype heterozygotes) induced IgG1 anti-BSA antibody responses that peaked 8 to 9 days after injection, and were more than 1000 times larger than those induced by injection of BSA alone, and 100 times larger than those induced by injecting unconjugated BSA plus H delta a/1. H delta a/1-BSA was no more immunogenic than unconjugated BSA when injected into CB20 mice, which express Ig of the b allotype, while AF3.33-BSA greatly enhanced anti-BSA antibody production in CB20, but not in BALB/c mice. Mice serially immunized with three different Ag conjugated to H delta a/1 made large antibody responses to all three Ag, provided that the mouse strain used did not recognize allotypic determinants on H delta a/1 as foreign and produce a neutralizing antibody response. Intravenous and s.c. routes of inoculation produced responses of similar magnitude and relatively low variability; responses to footpad or intramuscular inoculation were more variable, and i.p. inoculation induced smaller responses. Injection of BALB/c mice i.v. with 100 micrograms of H delta a/1-BSA induced an IgG1 anti-BSA response of 5.6 mg/ml, which was approximately 70% of the total IgG1 response. Anti-BSA responses to 30 micrograms of conjugate or less were much smaller, but could be considerably enhanced by adding unconjugated H delta a/1 to the inoculum. This system will be useful for the rapid stimulation of large antibody responses to biologically important Ag, and for investigating mechanisms of Ag processing and B and T cell activation.
Two distinct lymphocyte populations mediate simian immunodeficiency virus envelope-specific target cell lysis.
Authors: Yamamoto H , Miller M D , Watkins D I , Snyder G B , Chase N E , Mazzara G P , Gritz L , Panicali D L , Letvin N L 
Published: December 2022

Abstract
The relative contributions of the effector lymphocyte responses to the AIDS virus envelope glycoprotein (env) were explored in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. CD8+, MHC class I-restricted, env-specific CTL were cloned from PBL of SIVmac-infected monkeys, indicating that such cells constitute a component of the env-specific effector lymphocyte response. A limiting dilution 51Cr release assay was then established for quantitating the frequency of SIVmac-specific effector lymphocytes in PBL of rhesus monkeys. Using this assay we demonstrate that SIVmac env-specific effector lymphocytes are comprised of both CD16-, MHC class I-restricted and CD16+, MHC class I-unrestricted cells. We also demonstrate that the env-specific response is the predominant SIVmac-specific effector lymphocyte response in rhesus monkeys. These studies document the complexity of the effector lymphocyte response to the AIDS virus envelope glycoprotein and establish the role played by two distinct effector cell populations in this response.
Independent regulation of IFN-gamma and tumor necrosis factor by IL-1 in human T helper cells.
Authors: Fischer H , Hedlund G , Kalland T , Sjögren H O , Dohlsten M 
Published: December 2022

Abstract
The lymphokines IL-2 and IL-4 promoted the growth of human PHA-triggered T cells, but only IL-2 induced the production of IFN-gamma and TNF. The addition of purified monocytes strongly enhanced the production of IFN-gamma in IL-2-stimulated T cell cultures but did not influence the production of TNF or the level of T cell proliferation. The addition of IL-1 to T cells activated by PHA and optimal concentrations of IL-2 resulted in a strong induction of IFN-gamma production but had no influence on TNF production or T cell proliferation. IL-6 did not influence IFN-gamma or TNF production or T cell proliferation induced by PHA-IL-2 and did not modulate IL-1-induced IFN-gamma production. The production of IFN-gamma by CD4+ 45R+ Th cells was strongly enhanced by IL-1, whereas CD8+ T cells were less responsive to IL-1 and CD4+ 45R+ T cells were unresponsive to IL-1. We demonstrate, at the clonal level, that the optimal production of IFN-gamma by human Th cells requires both IL-1 and IL-2, whereas the production of TNF and T cell proliferation are induced by IL-2 alone. We suggest that IL-1 acts as a second signal for IFN-gamma production and that it may have an important function in regulating the pattern of lymphokines produced by T cell subsets during activation.
Mapping of epitopes on the La(SS-B) autoantigen of primary Sjögren's syndrome: identification of a cross-reactive epitope.
Authors: McNeilage L J , Macmillan E M , Whittingham S F 
Published: December 2022

Abstract
Autoepitopes on the ribonucleoprotein La(SS-B) were identified by using recombinant La(SS-B) polypeptides and sera from 166 patients with the antinuclear autoantibody anti-La(SS-B). The La(SS-B) polypeptides were encoded by polymerase chain reaction-derived overlapping or nonoverlapping fragments of the La(SS-B) gene, which encodes a protein of 408 amino acids (aa). Of the 166 sera tested, 99% reacted with a fusion protein comprising the first 107 N-terminal aa (LaA); 91% reacted with a fusion protein comprising aa 111 to 242 (LaC), and 91% reacted with a fusion protein comprising aa 346 to 408 (LaL2/3) at the C terminus of La(SS-B). The order of immunodominance as assessed by the number of sera reacting with each epitope and the strength of the reactivity was LaA (aa 1 to 107) greater than LaC (aa) 111 to 242) much greater than LaL2/3 (aa 346 to 408). Cross-reactivity was observed between antibodies eluted from LaC (aa 111 to 242) and LaL2/3 (aa 346 to 408), but there was no significant primary sequence homology between the two regions. The LaC region contained at least two epitopes, one encompassing a putative RNA-binding motif (aa 112 to 187) which was recognized by 83% of patient sera. Serial serum samples from three patients showed that the antibody response to La(SS-B) was initially directed to the N terminus (LaA, aa 1 to 107), but over a period of time all three major epitopes, including that encompassing the putative RNA-binding motif, were recognized. This result suggests that the primary immune response to La(SS-B) is restricted to an immunodominant epitope. As the specificity of the autoantibody response broadens, it includes the RNA-binding motif, which may have important implications for the expression of disease.