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

We have examined fetal thymic development in the trisomy 16 (Ts16) mouse, which is considered to be a model for human trisomy 21, or Down Syndrome. The Ts16 thymus contains 10 to 20% of the number of lymphocytes found in a normal thymus at a comparable stage. Expression of thymocyte differentiation markers (Thy-1, CD5, CD8, CD4, CD3, and HSA) is severely affected in Ts16 fetuses aged 14-18 gestational days. When thymuses from 14-day Ts16 mice were cultured in vitro, these markers eventually reached levels of expression comparable to those seen in normal thymuses in culture. On the other hand, expression of CD44 appears to be unaffected in Ts16 thymuses in vivo, but declines in vitro relative to normal thymuses. Reconstitution of depleted thymic stroma with thymocytes showed evidence of defects in both developmental compartments.
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PMID:Defects in thymocyte differentiation and thymocyte-stromal interactions in the trisomy 16 mouse. 137 32

In a previous study, we raised a mAb (MTS 35) reacting with a plasma membrane Ag expressed on both cortical thymocytes and a subset of thymic medullary epithelial cells. In view of the shared expression of this molecule, we have defined it as thymic shared Ag-1 (TSA-1). Considering its selective reactivity with cortical, but not medullary thymocytes, the relevance of TSA-1 as a marker of immature T cells was investigated in detail in this study, using multicolor flow cytometric analysis. TSA-1 was found on all immature thymocyte subsets (CD3-4-8-, CD3-4+8-, CD3-4-8+, CD3-4+8+, CD3low4+8+). Conversely, CD3high4+8- and CD3high4-8+ thymocytes, early thymic migrants and peripheral T cells were TSA-1-. More refined gating and analysis of the transitional CD3intermediate/high4+8+ thymocytes, proposed candidates for negative selection, demonstrated that approximately one half were TSA-1-. In fact, there was a directly inverse relationship between TSA-1 and CD3 expression on thymocytes. In the periphery, TSA-1 was detected on B lymphocytes. TSA-1 is PI-linked and has a molecular mass of 17 kDa nonreduced, or 12 to 13 kDa reduced. Through cross-correlation analysis, this molecule was distinct from H-2K, PNA-R, CD5, CD11a/18, Thy-1, HSA, Ly6A/E, Ly6C, ThB, CD25, CD44. Hence TSA-1 appears to be a unique marker which exquisitely separates mature from immature thymocytes.
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PMID:Thymic shared antigen-1. A novel thymocyte marker discriminating immature from mature thymocyte subsets. 153 95

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

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

Cell sorting and cytotoxic depletion procedures were used to subdivide the population of CD4- CD8- ("double-negative") thymocytes from adult CBA mice on the basis of expression of Ly-1, HSA (the "heat-stable antigen" M1/69 or B2A2), Pgp-1 glycoprotein, Thy-1, MEL-14 and the PC61 antigenic determinant on the IL2 receptor (IL2R). The level of dividing cells within these subsets was assessed by brief in vivo administration of [3H]-thymidine, followed by radioautography, or by flow cytometric cell cycle analysis after DNA staining. The capacity of the subsets to proliferate in culture, in response to stimulation with concanavalin A (Con A), or with phorbol myristate acetate (PMA) and the calcium ionophore ionomycin, was assessed in high cloning efficiency single-cell culture systems. In general, the proliferative response in culture was inversely related to the rate of cell division in vivo. Response of the double-negative subsets to Con A correlated with expression of the T cell antigen receptor complex; although a high cloning efficiency was obtained from the receptor-positive fractions, very few of the clones were cytotoxic. In particular, a major Ly-1+ HSA- Pgp-1+ double-negative subset, as well as minor Ly-1- HSA- Pgp-1+ subsets, contained very few cells in cycle in vivo, but showed a high cloning efficiency in both culture systems. Conversely, the other major double-negative subset, Ly-1- HSA+ Pgp-1-, included most of the cells in cycle, but showed a reduced cloning efficiency in response to PMA and ionomycin and failed to respond to Con A. The dividing cells within the Ly-1- HSA+ Pgp-1- group were strongly enriched in the IL2R- rather than in the IL2R+ subset, suggesting IL2 was not the growth factor maintaining their proliferation in vivo.
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PMID:Subpopulations of CD4- CD8- murine thymocytes: differences in proliferation rate in vivo and proliferative responses in vitro. 289 96

Four thymic epithelial cell lines (TEC) were derived from neonatal CBA and non-obese diabetic (NOD) mouse thymus. From these cell lines a series of clones were produced by limit dilution and these have remained in stable culture for more than 1 year. Morphological characterization indicates that most cells are stellate with numerous short or long processes and ultrastructural studies show both active and quiescent cells with junctional complexes and bundles of tonofibrils. Immunohistochemical and flow cytometric analyses show that the cells express cytokeratin and appear to label for markers characteristic of cortical epithelial cells. Most clones express Thy-1, Pgp-1, ICAM-1, HSA and B220 antigen, but are negative for LFA-1, CD2, Mel 14, Fc receptor, Mac-1, CD4 and CD8. All clones express low to moderate levels of class I MHC but are either negative or extremely low for class II MHC antigen. Most clones secrete IL-6 and granulocyte-macrophage-CSF (GM-CSF) in vitro, but generally do not produce IL-2, IL-3, IL-4 or IFN-gamma.
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PMID:Production and characterization of mouse thymic epithelial cell clones. 751 33

L1 is a transmembranal homophilic cell adhesion molecule of the immunoglobulin superfamily expressed by neural and lymphoid cells. The heat-stable antigen (HSA, murine CD24) nectadrin is a highly and heterogeneously glycosylated glycophosphatidylinositol-linked differentiation antigen of haematopoietic and neural cells. L1 and nectadrin have been shown to mediate cell adhesion and intracellular Ca2+ signals in neurons and B lymphoblasts, respectively. Here we show that nectadrin is co-expressed with L1 in murine cerebellar granule cell neurons and neuroblastoma N2A cells. Purified nectadrin bound to L1 with an apparent binding ratio of five nectadrin molecules to one L1 molecule at saturation. Binding between nectadrin and purified N-CAM was not observed. In co-capping experiments nectadrin co-redistributed with L1 and N-CAM. Since in these cells N-CAM and L1 cohere by cis-binding nectadrin appears to join the L1-N-CAM complex through binding to L1. Antibodies to each L1 and nectadrin evoked small increases in the intracellular Ca2+ concentration. However, when both antibodies were added together or in tandem to the cells, a strong intracellular Ca2+ signal was measured that was at least 6- and 10-fold stronger than the signal separately induced by L1 and nectadrin antibodies respectively. Such a cooperative effect was not observed in B lymphoblasts, using the same antibodies, or in neurons, using a combination of L1 and Thy-1 antibodies. Both the weak Ca2+ signal mediated by L1 alone and the enhanced signal jointly triggered by antibodies to L1 and nectadrin were inhibited by phorbol 12-myristate 13-acetate and were not significantly affected by Ni2+ and Cd2+ cations, suggesting that they are related to one another and involve recruitment of intracellular Ca2+. Nectadrin therefore appears to join a functional complex of neuronal adhesion molecules and to potentiate the signal transduction pathway of L1, possibly in response to neuron-neuron contact formation.
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PMID:Evidence for cis interaction and cooperative signalling by the heat-stable antigen nectadrin (murine CD24) and the cell adhesion molecule L1 in neurons. 761 34

Whole body irradiation produces profound thymic atrophy. After sublethal irradiation, regeneration begins promptly and the earliest regeneration is from radioresistant intrathymic precursors. The progeny of these precursors expand rapidly and restore thymic cellularity to near normal within 2 weeks. We have used monoclonal antibodies specific for a variety of differentiation markers of the T lineage to analyze the early events in thymic regeneration. A three-color flow microfluorometric analysis revealed that the majority of the cells found early in the regenerative process have the phenotype of mature T cells. These include CD4-/CD8-; CD3hi as well as CD4+/CD8-; CD3hi and Cd4-/CD8+; CD3hi. The proportion of cells with mature phenotypes declines rapidly between day 6 and day 12. Not all of the early appearing cells have mature phenotypes. Among the early cells that do not express CD3 are both CD4 and CD8 single positive cells that express HSA and resemble the intrathymic precursors found in other systems. In these mice CD4 single positive predominate. There are other cells that are HSA positive but express low levels of CD4 and very low levels of Thy-1. These appear to include the earliest members of the T-lineage. In addition to relatively mature conventional T cells and early progenitors, the early developing population includes cells that express markers of the T-cell lineage including the T-cell receptor but do not express Thy-1. These Thy-1 negative T cells comprise a significant number of the earliest cells found after regeneration.
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PMID:Early thymic regeneration after irradiation. 800 3

The development of T cells belonging to the gamma delta lineage is not well understood. We have analyzed the cells in the adult murine thymus which express the gamma delta TcR on the surface in order to learn more about this process. Our data demonstrate a number of clear subpopulations of gamma delta expressing cells in the thymus based on the expression of Thy-1 and HSA (heat-stable antigen). Only one of these subpopulations, the one expressing both Thy-1 and HSA, contains dividing cells or has a significant rate of turnover. Together with the fact that emigrant gamma delta cells are HSA+Thy-1+, this suggests that this thymic subpopulation is the sole, or major, source of exported cells. However, the turnover of cells from this population is 5 x 10(4) - 10 x 10(4) cells per day, while previous estimates of the rate of export of gamma delta cells are in the order of 10(4) cells per day. Furthermore the V gamma profile of recent gamma delta+ emigrants differs from that of the thymic HSA+Thy-1+ cells. This raises the possibility that only a selected subpopulation of the thymic gamma delta+HSA+Thy-1+ population is exported, and that some gamma delta cells may die in situ in the thymus. The function of the other gamma delta thymic subpopulations, which are turning over very slowly or not at all, (i.e. the HSA-Thy-1- and HSA-Thy-1+ subpopulations) remains unclear.
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PMID:Development of gamma delta T cells in the adult murine thymus. 810 Jul 77

Immature CD4/CD8 double-positive (DP) thymocytes expressing self MHC-restricted TCR are positively selected in response to TCR signals to survive and differentiate into functionally competent CD4 or CD8 single positive (SP) T cells. In contrast, DP precursors expressing autoreactive TCR are clonally deleted in response to TCR signals. We show here that in vitro TCR engagement of TCR(low) DP thymocytes rapidly triggers a variety of events considered to be hallmarks of positive selection in vivo. These include increased expression of CD5 and Bcl-2, termination of RAG-1 and pre-T(alpha) gene expression, and a switch in lck promoter usage. We also demonstrate that CD4- or CD28-mediated signals synergize with TCR signals to induce these outcomes. Finally, we show that the response of DP thymocytes to TCR engagement is selective in that clonal deletion, CD4/CD8 lineage commitment, and other events associated with maturation, such as changes in expression of Thy-1, HSA, MHC class I, and CD45-RB, were not induced. Thus, only subsets of maturational processes associated with positive selection in vivo were shown to be directly coupled to TCR signaling pathways at the DP stage. These observations support conclusions from in vivo systems suggesting that multiple, temporally separated TCR engagements are required to effect the entire spectrum of developmental changes associated with positive selection, and provide a conceptual and experimental framework for unraveling the complexity of positive selection.
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PMID:TCR engagement of CD4+CD8+ thymocytes in vitro induces early aspects of positive selection, but not apoptosis. 897 76


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