Involvement of the interleukin 2 pathway in the rearrangement and expression of both alpha/beta and gamma/delta T cell receptor genes in human T cell precursors (original) (raw)
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Antigen-Specific CD3 +, CD4 -, CD8 - T Lymphocytes
Most antigen-specific peripheral murine T lymphocytes express the T cell differentiation antigens, CD4 or CD8, and a TCR composed ofa CD3-associated disulfidelinked heterodimer, TCR-a/(3 (1, 2). However, recent studies have identified a distinct population of CD3+,CD4-,CD8-cells that appear early in thymic ontogeny and are maintained in the mature thymus and the peripheral lymphoid organs throughout adult life . Immunoprecipitation studies of murine CD3 +,CD4-, CD8-T cells have shown that the majority of these cells do not express cell surface TCR a/a; rather their TCR complex includes a 45-kD S glycoprotein disulfide linked to either the TCRV y/Cylt gene product or the TCRV y/Cy4 gene product (demonstrated by immunoprecipitation with anti TCRy antisera) (5-7). These results suggested that the TCR-, y/8' cells may compose a separate lineage that develops in the thymus before the TCRa/R-expressing T cells .
Journal of Experimental Medicine
A small subset ofhuman peripheral Tlymphocytes express C133-associated receptor for antigen (TCR) composed of y and S chains (1). A remarkable phenotypic feature of most of these cells is the lack of surface expression of both C134 and C138 differentiation antigens, which are known to define the two major subsets of TCR a/(3+ cells (1). Recently, by the use of two anti TCRy/S mAbs (BB3 and STCS-1), we identified two distinct, nonoverlapping subsets of CD4-8-T cells (2, 3). Clonal analysis showed that cells reacting with BB3 mAb expressed disulphide-linked TCR, whereas expression of the non-disulphide-linked form ofTCR was always associated with STCS-1 reactivity. In both types of TCR-y/8, the y gene product displayed a molecular mass ranging between 41 and 44 kD. In no instance (>25 CD4-8-clones analyzed), could we detect the high molecular form (55 kD) ofthe y chain that had been previously revealed in a T cell leukemia (4) or in polyclonal cell lines derived from normal thymocytes (5) or from an immunodeficiency patient (1).
During fetal ontogeny, T cell progenitors entering the thymus undergo a coordinate pathway of differentiation . Discrete steps of intrathymic maturation can be monitored by the sequential appearance of cell surface glycoproteins, of which CD2 (711, sheep erythrocyte receptor) is thought to be the first T lineage-specific differentiation antigen (1). It is only after expression of CD2 that differentiating thymocytes proceed to acquire CD4 plus CD8 antigens, and finally segregate into two mutually exclusive subsets of CD2+CD3'CD4+CD8" and CD2+CD3+CD4-CD8+ mature thymocytes (1, 2). With the appearance of the CD3 molecular complex, thymocytes first express y/b and later a/o TCR heterodimers (3-5). This prevailing view of T cell ontogeny predicts that CD2 is expressed on all CD3 + T cells (1). Recently, however, CD2 -CD3 + T cells have been identified both in fetal human spleen and thymus (6), and in a subset of CD3 +TCRy/b+ peripheral blood T cells from one individual (7). In addition, CD2-stable variants have been selected from the CD3/TCR* leukemic Jurkat line (8). Together, these recently published data suggest that the expression of a functional CD3/TCR complex is not invariably linked to the simultaneous expression of the CD2 differentiation antigen.
Journal of Experimental Medicine
Most antigen-specific peripheral murine T lymphocytes express the T cell differentiation antigens, CD4 or CD8, and a TCR composed ofa CD3-associated disulfidelinked heterodimer, TCR-a/(3 (1, 2). However, recent studies have identified a distinct population of CD3+,CD4-,CD8-cells that appear early in thymic ontogeny and are maintained in the mature thymus and the peripheral lymphoid organs throughout adult life . Immunoprecipitation studies of murine CD3 +,CD4-, CD8-T cells have shown that the majority of these cells do not express cell surface TCR a/a; rather their TCR complex includes a 45-kD S glycoprotein disulfide linked to either the TCRV y/Cylt gene product or the TCRV y/Cy4 gene product (demonstrated by immunoprecipitation with anti TCRy antisera) (5-7). These results suggested that the TCR-, y/8' cells may compose a separate lineage that develops in the thymus before the TCRa/R-expressing T cells .
A small subset ofhuman peripheral Tlymphocytes express C133-associated receptor for antigen (TCR) composed of y and S chains (1). A remarkable phenotypic feature of most of these cells is the lack of surface expression of both C134 and C138 differentiation antigens, which are known to define the two major subsets of TCR a/(3+ cells (1). Recently, by the use of two anti TCRy/S mAbs (BB3 and STCS-1), we identified two distinct, nonoverlapping subsets of CD4-8-T cells (2, 3). Clonal analysis showed that cells reacting with BB3 mAb expressed disulphide-linked TCR, whereas expression of the non-disulphide-linked form ofTCR was always associated with STCS-1 reactivity. In both types of TCR-y/8, the y gene product displayed a molecular mass ranging between 41 and 44 kD. In no instance (>25 CD4-8-clones analyzed), could we detect the high molecular form (55 kD) ofthe y chain that had been previously revealed in a T cell leukemia (4) or in polyclonal cell lines derived from normal thymocytes (5) or from an immunodeficiency patient (1).
Human thymocytes expressing gamma/delta T-cell receptors
International Journal of Cancer, 1989
Expression of T-cell receptors of gammddelta type characterizes a small subset of peripheral T lymphocytes which is homogeneously composed of cytolytic cells and, in most instances, lack CD4 and CD8 differentiation antigens. By the use of anti-TCR gammddelta MAbs it is possible to identify two distinct subsets of TCR gammddelta+ cells that are characterized by a Cy l or Cy2-encoded forms of gamma-chain, respectively. While the 863 MAb-reactive (Cy l encoded) cell subset is prevalent in peripheral blood (PB), these cells represent < 10% in TCR gammddelta+ thymocyte populations. In thymus, the majority of cells was found t o react with delta-TCS I (or A13) MAbs. Culture of CD4-8-thymocytes (highly enriched in TCR gammddelta+ cells) in IL-2 resulted in the de novo expression of CD8 surface antigen and of non MHC-restricted cytolytic activity. Cloning of CD4-8thymocytes resulted, for the most part in CD3'TCR gammddelta+ cells. Moreover, the majority of clones expressed the unusual delta-TCS I +CD8+' phenotype and lysed the NK-sensitive K562 target cells. Analysis of the immunoprecipitated TCR molecules showed the existence of the (rare) heavy (55 kDa) form of gamma-chain. A redirected killing assay using murine P8I 5 target cells and appropriate "stimulatory" antibodies was further employed for functional analysis of thymus-derived TCR gammddelta+ clones. While anti-CD3 MAbs efficiently triggered the cytolytic activity of all clones irrespective of their phenotype, MAbs directed to TCR gammddelta induced efficient lysis only of BB3+ or delta-TCSI+CD8-clones, but not of delta-TCSI+CD8+ clones. Therefore, it appears that a receptor type which appears to be relatively inefficient in mediating activation signals is predominant in the thymus and rare in the periphery.