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CD3{varepsilon}-mediated signals rescue the development of CD4+CD8+ thymocytes in RAG-2 / mice in the absence of TCR {beta} chain expression
Authors:Shinkai, Yoichi   Alt, Frederick W.
Affiliation:Howard Hughes Medical Institute and the Departments of Genetics and Pediatrics, The Children's Hospital, and the Center for Blood Research, Harvard Medical School 300 Longwood Avenue, Boston, MA 02115, USA
Abstract:Recent studies have shown that TCR ß chain expressioncan effect the differentiation of CD4CD8 double-negative(DN) thymocytes to CD4+CD8+ double-positive (DP) thymocytes.The TCR ß chain is expressed on the surface of DPthymocytes in association with CD3{gamma}, {delta} and {varepsilon} chains, suggestinga potential role for CD3 components in this signaling process.We now report detection of a very tow level of surface expressionof CD3{varepsilon} on adult DN RAG-2–/–; thymocytes. This surfaceCD3{varepsilon} was associated with CD3{gamma} and {delta} chains, as detected by anti-CD3{varepsilon}immunoprecipitation analyses. Significantly, injection of anti-CD3{varepsilon}mAb into RAG-2–/– mice led to the accumulation ofan IL-2R{alpha} CD2+ DP cell population and a nearly 100-foldincrease in thymic cellularity to essentially normal levels.Together, these data strongly indicate that TCR ßchain-mediated developmental signals are transduced by CD3 componentsand provide potential insights into mechanisms by which TCRß chain expression may effect this process.
Keywords:gene targeting mouse   immune deficient mouse   immature T cells   signal transduction   thymocyte development
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