Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present report we describe a CD4+8- heat stable antigen-negative (HSA-) thymocyte subpopulation that expresses a distinguishably low density of alpha beta T-cell antigen receptors (TCRlo) from the majority of CD4+8- high-density TCR (TCRhi) mature-type thymocytes. This subpopulation appears relatively late in life. Analysis of MEL-14, Pgp-1 (CD44), ICAM-1 (CD54), and NK1.1 expression on this subpopulation revealed that the CD4+8- TCRlo population was a population having unique characteristics (MEL-14-, CD44+, ICAM-1+, and NK1.1+) compared to the CD4+8- TCRhi thymocytes, most of which are MEL-14+, CD44-, ICAM-1-, and NK1.1-. When TCR beta-chain variable region (V beta) usage was analyzed, this thymic population expressed predominantly products of V beta 7 and V beta 8.2 TCR gene families. Interestingly, cells with V beta 8.1 TCRs, which are reactive to Mls-1a antigens, were not eliminated from the CD4+8- HSA- TCRlo subpopulation but had been eliminated from the major CD4+8- HSA- TCRhi subpopulation in Mls-1a strains. A subset with a phenotype similar to the CD4+8- HSA- TCRlo thymocytes was also identified primarily in bone marrow, and this subset constituted approximately half of the CD4+ T cells in the bone marrow. The CD4+8- HSA- TCRlo cells showed extremely high proliferative responses to immobilized anti-TCR antibody but generated negligible responses to allogeneic H-2 antigens compared to the responses generated by the major CD4+8- HSA- CD3hi cells. However, the CD4+8- HSA- TCRlo cells in Mls-1b mice mounted vigorous proliferative responses to Mls-1a antigens but not in Mls-1a mice. The properties of this T-cell subset suggest that these cells belong to a lineage distinct from the major T-cell population.
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PMID:An NK1.1+ CD4+8- single-positive thymocyte subpopulation that expresses a highly skewed T-cell antigen receptor V beta family. 137 29

T cells expressing alpha beta- and gamma delta-TCR are associated with the murine vaginal epithelium. A combination of phenotypic analysis of cell surface Ag and molecular analysis of the gamma- and delta-genes was used to demonstrate that vaginal gamma delta-T cells have several features that distinguish them from gamma delta-T cells present in other tissues. Three color flow cytofluorometric analysis demonstrated that freshly isolated vaginal gamma delta-T cells are CD4-CD8- and their expression of Thy-1 is strain dependent. Furthermore, specific differences in CD5, CD28, and p55IL-2 receptor expression were found between alpha beta- and gamma delta-T cells isolated from vaginal tissue. The vaginal gamma delta-T cells are predominantly CD45+, pgp-1+, HSA-, Ly-6C-, and MEL-14-. Both alpha beta- and gamma delta-T cells were absent in vaginal tissue from nude mice, although Thy-1-positive cells are present. It was also demonstrated that V gamma 4 and V delta 1 are the only gamma- and delta-genes that are expressed by vaginal cells. Sequence analysis of their junctions revealed that they express the V gamma 4 and V delta 1 sequences also found in fetal thymocytes. Furthermore, the V delta 1 sequence is identical in the vaginal cells and the gamma delta-T cells from the epidermal epithelium. We conclude that the vagina, like the skin, is a site where gamma delta-T cells with an invariant TCR exist.
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PMID:Phenotypic analysis and gamma delta-T cell receptor repertoire of murine T cells associated with the vaginal epithelium. 167 35

Although peripheral naive cells only secrete IL-2 upon primary stimulation, their presumptive immediate precursors, HSAlow CD4+8- thymocytes, can produce a large amount of the set of lymphokines usually associated with preactivated or memory CD4+ lymphocytes: IL-4, IL-5, IL-10 and gamma-IFN. This phenotype can be attributed to true virgin thymocytes and not only to recirculating lymphocytes, because it is found in newborn thymuses and in fetal thymic organ culture. This mature stage of CD4+8- thymocytes is itself preceded by an immature stage (HSAhigh) where only IL-2 and small amounts of gamma-IFN can be elicited by the combination of calcium ionophore and phorbol ester, but not by TCR cross-linking. CD8+4- thymocytes pass through a similar immature HSAhigh stage, where their pattern of lymphokine secretion is not yet differentiated from that of CD4+8- HSA high thymocytes. The subsets acquire their specific profiles at the HSAlow stage. We propose that recent thymic CD4+8- emigrant cells include a significant proportion of Th0 type cells, and that their role is critical to prime the immune system for IL-4 production, as well as to explain the longstanding observations of synergy between helper cell subpopulations in the periphery.
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PMID:Th0 cells in the thymus: the question of T-helper lineages. 168 78

These experiments were designed to evaluate the role of cytokines in early T cell development within the thymus. By using a thymic organ culture model, we have studied the influence of high dose of IL-2 (10 to 1000 IU/ml) on the cell populations that are generated during 12 days starting from a thymic rudiment of 14-day-old mouse embryo. The IL-2 treatment resulted in the expansion of Thy-1+/-, CD4-, CD8-, CD3-, Fc gamma RII+, CD5 (Lyt-1)-, HSA-, Pgp- 1+, Mel-14- population. These cells had the morphology of large granular lymphocytes and displayed broad cytotoxic activity. In addition, IL-2-treated organ cultures had a dramatic decrease in CD4+CD8+ thymocytes, a marked reduction in TCR-alpha beta+ thymocytes--even more pronounced in the TCR-V beta 6+ and TCR-V beta 8+ thymocytes--and no significant changes in the number of TCR-gamma delta+ as compared to control organ cultures.
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PMID:Expansion of large granular lymphocytes in IL-2-driven 14-day-old fetal thymocytes in organ culture. 197 May 91

Mice homozygous for either of two autosomal recessive mutations, lpr and gld, develop massive, generalized lymphoproliferation of CD4-CD8- (double negative, DN) T cells associated with a variety of autoantibodies. To determine the origin of these expanded populations of lpr and gld T cells, we examined the expression of CD2 molecules and mRNA transcripts in association with other cell surface phenotypes of these cells and correlated them with subpopulations of DN T cells in the thymus and peripheral lymphoid tissues. The results indicated that both lpr and gld cells are negative for the transcript and product of the CD2 gene. Both lpr and gld DN T cells were CD2-, CD3+, CD4-, CD8-, CD25-, CD45R+, TCR alpha/beta+, TCR gamma/delta-, HSA(J11d)-/+, Thy-1+/-, and Lp-1-/+. Studies of thymocytes in normal mice using three-color flow cytometry analysis showed that there are at least eight phenotypically distinct populations of DN thymocytes, one of which is similar to lpr and gld cells in terms of CD2-, CD3+, TCR alpha/beta+ and CD25- phenotypes, although they did not express CD45R, HSA, or Lp-1. A very minor population of these CD2-CD3+ TCR alpha/beta+ DN T cells were also detected in peripheral T cells from normal mice. These findings may provide insight into not only the origin of the aberrant lpr and gld T cells but also normal T cell development.
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PMID:The expanded populations of CD4-CD8- T cell receptor alpha/beta+ T cells associated with the lpr and gld mutations are CD2-. 197 May 92

T cell antigen receptor expression by cycling and post-cycling thymocytes has been analysed by flow cytometry. Normal mice were pulsed with 5-bromo-2'-deoxyuridine (BrdUrd), a thymidine analogue detectable with a monoclonal antibody. Thymocytes were surface-stained with antibodies against several V beta gene products and against whole alpha beta receptors and detection of BrdUrd in the nuclei was performed after enzymatic generation of single-stranded DNA. A significant (10%) percentage of thymocytes expressing high levels of alpha beta TCR were found in the cycle: these cells were immature, as shown by the CD4+8+ phenotype and by high HSA expression. After division, most alpha beta high BrdUrd+ cells entered a resting state and their number remained constant for 3 days, decreasing in two steps thereafter. This post-mitotic evolution was not modified by injection of an anti-mitotic drug. After day 4, a majority of the studied subset acquired a single positive phenotype. Location of BrdUrd+ V beta 8.2 high cells studied on frozen sections was found cortical at early times and medullary after day 3. V beta 6 expression by cycling and post-cycling thymocytes was analysed in various mouse strains, and early high expression by cycling thymocytes was found to be restricted to MIs 1b strains. These results suggest that high alpha beta TCR expression by cycling immature thymocytes corresponds to positive selection, which must therefore be considered as an early event in intrathymic differentiation.
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PMID:Positive selection is an early event in thymocyte differentiation: high TCR expression by cycling immature thymocytes precedes final maturation by several days. 214 65

Murine CD3+,CD4-,CD8- peripheral T cells, which express various forms of the TCR-gamma delta on their cell surface, have been characterized in terms of their cell-surface phenotype, proliferative and lytic potential, and lymphokine-producing capabilities. Three-color flow cytofluorometric analysis demonstrated that freshly isolated CD3+,CD4-, CD8- TCR-gamma delta lymph node cells were predominantly Thy-1+,CD5dull,IL-2R-,HSA-,B220-, and approximately 70% Ly-6C+ and 70% Pgp-1+. After CD3+,CD4-,CD8-splenocytes were expanded for 7 days in vitro with anti-CD3-epsilon mAb (145-2C11) and IL-2, the majority of the TCR-gamma delta cells expressed B220 and IL-2R, and 10 to 20% were CD8+. In comparison to CD8+ TCR-alpha beta T cells, the population of CD8+ TCR-gamma delta-bearing T cells exhibited reduced levels of CD8, and about 70% of the CD8+ TCR-gamma delta cells did not express Lyt-3 on the cell surface. Functional studies demonstrated that splenic TCR-gamma delta cells proliferated when stimulated with mAb directed against CD3-epsilon, Thy-1, and Ly-6C, but not when incubated with an anti-TCR V beta 8 mAb, consistent with the lack of TCR-alpha beta expression. In addition, activated CD3+,CD4-,CD8- peripheral murine TCR-gamma delta cells were capable of lysing syngeneic FcR-bearing targets in the presence of anti-CD3-epsilon mAb and the NK-sensitive cell line, YAC-1, in the absence of anti-CD3-epsilon mAb. Finally, activated CD3+, CD4-,CD8-,TCR-gamma delta+ splenocytes were also capable of producing IL-2, IL-3, IFN-gamma, and TNF when stimulated in vitro with anti-CD3-epsilon mAb.
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PMID:Phenotypic and functional analysis of murine CD3+,CD4-,CD8- TCR-gamma delta-expressing peripheral T cells. 252 34

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

Transgenic (TG) mice with TCR alpha and beta chain genes from a CD4-dependent auto-I-Ak reactive T cell clone were generated. H-2k TG mice had a large number of thymic and splenic CD4 T cells expressing the autoreactive TCR without manifestation of autoimmunity. The cells were not anergic, as they could respond to autologous antigen presenting cells and anti-TCR antibodies in vitro to proliferate and to produce interleukins. Various degrees of down-regulation of CD2 and CD44 was observed in TG mice, indicating the presence of a defective co-stimulatory process in TG T cells. These features indicate that the self tolerance in autoreactive TCR TG mice is due not to clonal deletion and anergy but to a novel mechanism where T cells cannot sufficiently respond to normally existing self ligand in vivo. That such an in vivo unresponsiveness of autoreactive T cells is dictated in the thymus during CD4 T cell differentiation atypical form of positive selection of autoreactive T cells was suggested by the abnormal surface expression of CD69 and HSA.
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PMID:A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCR alpha and beta chain genes. 801 99

Thymectomy of 3-day-old mice induces organ-specific autoimmune disease. To define a relationship between the development of T cells early in the neonatal period and autoimmunity, we studied the thymus and peripheral lymphoid tissues of 3-day-old mice. Lymph nodes, but not spleens, of 3- to 4-day-old mice contained a significant number of thymus-derived CD4+CD8+ cells that are phenotypically similar to CD4+CD8+ thymocytes in their level of expression of CD3 and HSA. It is likely that the prematurely exported cells are the progenitors of autoreactive T cells because the lymph nodes from 3- to 4-day-old male, but not female, mice which express a transgenic TCR specific for the H-Y Ag contained a large number of CD4+CD8+Tg+ as well as CD4-CD8+Tg+ T cells. Thus, the neonatal thymus is capable of exporting immature T cells that in the absence of a thymus may differentiate into autoimmune effector cells.
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PMID:Premature escape of double-positive thymocytes to the periphery of young mice. Possible role in autoimmunity. 812 Mar 65


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