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  • Altered Development of CD8 ...
    Broussard, Christine; Fleischecker, Christine; Horai, Reiko; Chetana, Madeva; Venegas, Ana M.; Sharp, Leslie L.; Hedrick, Stephen M.; Fowlkes, B.J.; Schwartzberg, Pamela L.

    Immunity (Cambridge, Mass.), 07/2006, Letnik: 25, Številka: 1
    Journal Article

    Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca 2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection. Itk −/− and Rlk −/−Itk −/− mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8 + T cells in these mice do not resemble conventional CD8 + T cells. Instead, these cells express memory markers, rapidly produce interferon-γ, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted “innate-type” lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8 + T cell phenotypes in Itk −/− mice, arguing that altered signaling permits development of this innate-type CD8 + cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.