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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymph node cells from C3H mice homozygous for lpr and gld were compared for expression of cell surface antigens, lectin-binding sites, functional characteristics, expression of ecotropic MuLV, and organization of Ig and T cell receptor (TcR) beta-chain genes. The abnormal cells (Ly-2-/L3T4-) populating nodes of both mutant strains were specifically purified by using plate separation techniques. The purified abnormal cells were shown to express the beta-chain of the TcR, to exhibit rearrangements of the beta-chain genes, and to express TcR beta and alpha gene mRNA, demonstrating the T cell origin of these populations. FMF analyses of the separated abnormal cells showed them to be Thy-1+, Ly-1+, Ly-2-, L3T4-, Ly-5(B220)+, Ly-6+, Ly-22+, Ly-24+, sIg-, ThB-, Ia-, HSA-/+, and PC.1+ and to bind at high levels lectins that normally bind preferentially to B cells. These cells did not proliferate or generate CTL in response to stimulation with alloantigens, and supernatants of cells stimulated with Con A were devoid of IL 2. These characteristics do not correspond to those of any known immature or mature population of normal T cells. The findings that the abnormal T cells of lpr and gld homozygotes are indistinguishable for each parameter examined support the suggestion that these mutations may affect different enzymes in a common metabolic pathway of major importance to T cell differentiation and function.
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PMID:Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. 300 14

Optimal activation of T cells often requires signals delivered by the ligation of T cell receptor (TcR) and those resulting from costimulatory interaction between certain T cell surface accessory molecules and their respective counter receptors on antigen presenting cells. The molecular events underlying the co-stimulatory activity are still not understood fully. Here we describe a 38-42-kDa (B3) protein, present on the surface of lipopolysaccharide-activated B cells, which can provide co-stimulation to resting T cells leading to a predominant release of interleukin (IL)-4 and IL-5 and negligible amounts of IL-2 and interferon-gamma. Binding assay and electron microscopic autoradiography data suggest that this molecule binds T cells, and the same can be competed by unlabeled B3. Characterization experiments point out that B3 shows up as a single prominent peak on reverse phase-high performance liquid chromatography, runs as a single spot in reducing two-dimensional gel electrophoresis, and is a phosphoglycoprotein. The Western analysis indicate that it does not cross-react with antibodies directed against murine ICAM-1, LFA-1 alpha, VCAM-1, HSA, and B7 suggesting the novelty of the protein. The internal amino acid sequence of this molecule suggests that it does not belong to a known category of murine B cell surface molecules.
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PMID:Characterization of novel costimulatory molecules. A protein of 38-42 kDa from B cell surface is concerned with T cell activation and differentiation. 755 3

The introduction and expression of allogeneic MHC class I genes in tumors can generate tumor-specific immunity which subsequently results in the regression of parental tumors. Immunization of naive (AKR/J x C57BL/6)F1 mice with H-2Kb-transformed K36 tumor cells was found to render recipient mice immune to a subsequent challenge by parental K36 tumor cells. Two types of cytotoxic T effector cells were demonstrated in these immune mice. One of the cytotoxic effector cells generated against the K36 tumor cells is the conventional CD3+ cells, and these account for approximately one-third of the total observed tumor-specific cytotoxicity in vitro. The other cytotoxic effector cell generated following the immunization of (AKR/J x C57BL/6)F1 mice with the H-2Kb-transformed K36 cells had the CD3-/Thy-1+ phenotype, and accounted for the remaining two-thirds of the observed tumor-specific cytotoxicity in vitro. These CD3-/Thy-1+ cells can lyse parental K36 tumor cells in a tumor-specific fashion, and tumor-specific immunity can be adoptively transferred to naive animals via the CD3-/Thy-1+ cells. In contrast to CD3+ CTL, CD3-/Thy-1+ cells express CD45RBlow, Ly-6Chigh, and HSA molecules. Although the CD3-/Thy-1+ cells can be activated in vitro by IL-2, TPA, and ionomycin, they cannot be propagated in vitro. The CD3-/Thy-1+ cells undergo apoptosis following prolonged culture in vitro. At present, the exact mechanism(s) by which CD3-/Thy-1+ cells can mediate tumor-specific cell lysis in the absence of identifiable T cell receptor molecules is unknown; nevertheless, these data suggest the existence of a novel T cell type to combat tumors.
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PMID:Characterization of tumor-specific cytotoxic effector cells with a novel CD3-/Thy-1+ phenotype. 758 74

We have studied the differentiation and repertoire selection during the maturation of CD4+CD8+ (DP) thymocytes into CD4+CD8- (CD4SP) and CD8+CD4- (CD8SP) T cells, in normal mice, mice transgenic for T cell receptor (TcR)-alpha beta restricted by either class I or class II major histocompatibility (MHC), and in mice deficient in class I or class II MHC expression. Our data suggest that mature CD4 and CD8 T cells derive from different pathways of T cell differentiation in the thymus. Thus, interaction of DP thymocytes with MHC class II leads to the immediate down-regulation of CD8, which occurs simultaneously with an increase in TcR expression; DPTcR(lo)HSA(hi) thymocytes mature into a CD4+CD8(lo) TcR(hi)HSA(hi) intermediate population. This cell population generates CD4SP thymocytes, the majority of which are still HSA(hi). In contrast, interaction with MHC class I induces the up-regulation of TcR, which precedes the down-regulation of CD4; DPTcR(lo) generate DPTcR(hi) thymocytes, the majority of which are the committed precursors of CD8SP cells. Further differentiation results in CD4 down-regulation and the transition from DPTcR(hi) into CD8+CD4(lo) TcR(hi)HSA(lo) and +D8SPTcR(hi)HSA- T cells. Since down-regulation of CD4 and CD8 occurs at different stages of thymocyte differentiation, our results do not support a stochastic/selective model of lineage commitment in the thymus.
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PMID:Generation of mature T cell populations in the thymus: CD4 or CD8 down-regulation occurs at different stages of thymocyte differentiation. 791 76

1-2% of adult mouse thymocytes express the T cell receptor alpha/beta (TCR-alpha/beta) together with the interleukin (IL) 2R beta (p70), but not the alpha (p 55) chain. We show that the previously described alpha/beta-TCR +CD4-8- and the partially overlapping Ly6C+ thymocytes are contained within this subset. Most IL-2R beta+ alpha/beta-TCR+ cells have a mature and activated (heat stable antigen [HSA]-, thymic shared antigen 1 [TSA-1]-, CD44high, CD69+) phenotype. Overrepresentation of V beta 8.2 in both CD4-8- and CD4 and/or CD8+ IL-2R beta+ thymocytes suggests that IL-2R beta expression is induced by a TCR-mediated activation event. In mice transgenic for an H-2Kb-specific TCR, IL-2R beta+ cells were abundant under conditions of mainstream negative selection, i.e., in the presence of Kb, but absent under conditions of mainstream positive selection or in a nonselecting environment. Together, these results show that in addition to clonal deletion, self-recognition by immature thymocytes leads to phenotypic maturation of a small subset of thymocytes expressing IL-2R beta. IL-2-deficient mice contain normal numbers of IL-2R beta+ alpha/beta-TCR+ thymocytes, indicating that like mainstream T cell development, this minor pathway of positive selection does not depend on IL-2. However, in the absence of IL-2, the CD4/CD8 subset composition of IL-2R beta+ thymocytes is skewed towards CD4-8+, mostly at the expense of CD4-8-. A possible relevance of this finding for the development of the immune pathology of IL-2-deficient mice is discussed.
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PMID:Induction of interleukin 2 receptor beta chain expression by self-recognition in the thymus. 796 50

The initiation of T cell responses against antigens requires two distinct signals. The first, the essential signal is the engagement of T cell receptor to antigen peptide in the context of MHC molecules on antigen presenting cells (APC). The presence of the second signal (costimulatory signal) determines whether responding T cells to be fully responsive or to be anergic (antigen specific nonresponsiveness). There are numbers of such costimulatory receptor/ligand pairs including B7/CD28: CTLA4, VCAM-1/VLA4, ICAM-1/LFA-1, HSA/unknown, and LFA-3/CD2. Among those ligand receptor pairs, B7/CD28 pathway is chosen and the molecular mechanism how T cell responses are regulated by B7/CD28 is discussed.
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PMID:[The molecular mechanism of costimulatory signal for T cell activation]. 853 79

Optimal activation of T cells to clonally expand requires at least two distinct biological signals; one is generated by the interaction of the T cell receptor (TcR) with peptides bound to MHC molecules. The other signal(s) is (are) generated by a functionally defined event called the co-stimulatory pathway. We have characterized the co-stimulatory property of a murine B lymphocyte membrane protein (155-160 kD) on resting CD4+ T cells. The study involved the isolation of a 155-160 kD protein (B1) from the membranes of LPS-stimulated B cells. When reconstituted into lipid vesicles, B1 exerted a dose-dependent proliferative response to CD4+ T cells, resulting in the predominant secretion of IL-4 and IL-5 after cross-linking receptors with anti-CD3 mAb. This protein is a phosphoglycoprotein which gives a single spot on two-dimensional gel electrophoresis under reducing conditions and as a distinct peak on reverse phase-HPLC. The B1 binds to the T cell surface as is demonstrated by electron microscopic autoradiography and scanning electron microscopy, as well as competitive binding assays. It does not cross-react with antibodies directed against ICAM-1, LFA-1 alpha, B7, HSA and VCAM-1, suggesting the novelty of the protein. Activation of CD4+ T cells with B1 in the presence of anti-CD3 resulted in the translocation of protein kinase C (PKC). The B1 is barely detectable on the surface of resting B cells and digestion of this protein with V8 protease and peptide N-glycosidase F resulted in distinct protein bands on an autoradiogram.
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PMID:Characterization of a novel co-stimulatory molecule: a 155-160kD B cell surface protein provides accessory help to CD4+ T cells to proliferate and differentiate. 860 18