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  • Title: Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes.
    Author: Fischer KD, Zmuldzinas A, Gardner S, Barbacid M, Bernstein A, Guidos C.
    Journal: Nature; 1995 Mar 30; 374(6521):474-7. PubMed ID: 7700360.
    Abstract:
    During lymphocyte development, cellular proliferation and positive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors. These processes are initiated when engagement of growth-factor receptors, or the T and B lymphocyte antigen receptors, induces tyrosine phosphorylation of specific SH2- and SH3-domain-containing cytoplasmic proteins, including Vav. Here we show that vav-/- embryonic stem cells generate only limited numbers of immature and mature T and B lymphocytes in the RAG-2 blastocyst complementation assay. Furthermore, Vav-deficient T lymphocytes showed severely impaired antigen receptor signalling. Finally, we demonstrate that Vav-dependent signalling pathways regulate maturation, but not CD4/CD8 lineage commitment, during T-cell-receptor-mediated positive selection of immature CD4+ CD8+ precursors into mature CD4+ CD8- or CD4- CD8+ T cells.
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