Abstract
The Tec family tyrosine kinases, Itk and Rlk, are expressed in thymocytes and peripheral T cells and regulate thresholds of T cell receptor signaling. Yet little is known about the specific role of Itk- and Rlk-dependent signals in CD8(+) T cell maturation. We show here that Itk(-/-) and Rlk(-/-)Itk(-/-) mice were nearly devoid of conventional CD8(+) T cells and, instead, contained a large population of CD8(+) T cells that bear striking similarity to lineages of innate lymphocytes. Itk(-/-) and Rlk(-/-)Itk(-/-) CD8(+) thymocytes and T cells were CD44(hi), CD122(+), and NK1.1(+); were able to produce interferon-gamma directly ex vivo; and were dependent on interleukin-15. Itk(-/-) and Rlk(-/-)Itk(-/-) CD8(+) thymocytes expressed abundant transcripts for the T box transcription factor, eomesodermin, correlating with their phenotype and function. These data indicate a critical role for Itk and Rlk in conventional CD8(+) T cell development in the thymus.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / enzymology*
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation*
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Cell Proliferation
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Cells, Cultured
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Hyaluronan Receptors / metabolism
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Immunologic Memory / immunology
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Interleukin-15 / deficiency
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Interleukin-15 / genetics
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Interleukin-15 / metabolism
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phenotype
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Protein-Tyrosine Kinases / classification
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Protein-Tyrosine Kinases / deficiency
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Antigen, T-Cell / metabolism
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T-Box Domain Proteins / metabolism
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Time Factors
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Up-Regulation
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Xenopus Proteins / metabolism
Substances
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EOMES protein, Xenopus
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Hyaluronan Receptors
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Interleukin-15
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Receptors, Antigen, T-Cell
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T-Box Domain Proteins
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Xenopus Proteins
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Tec protein-tyrosine kinase
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase