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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk.

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-gamma, 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.[1]


  1. Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk. Broussard, C., Fleischecker, C., Horai, R., Chetana, M., Venegas, A.M., Sharp, L.L., Hedrick, S.M., Fowlkes, B.J., Schwartzberg, P.L. Immunity (2006) [Pubmed]
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