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T cell development and function in CrkL-deficient mice.

Amy C Peterson·Reinhard E Marks·Patrick E Fields·Akira Imamoto·Thomas F Gajewski
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Abstract

The adapter protein CrkL has been implicated in multiple signal transduction pathways in hematopoietic cells. In T lymphocytes, the recruitment of CrkL-C3G complexes has been correlated with hyporesponsiveness, implicating CrkL as a potential negative regulator. To test this hypothesis we examined T cell activation in CrkL-deficient mice. The CrkL(-/-) genotype was partially embryonic lethal. In viable CrkL(-/-) mice, peripheral blood counts were normal. The thymus from CrkL(-/-) mice had 40% fewer cells compared to littermates, but the proportion of thymocyte subsets was comparable. There was no discernable alteration in T cell function as reflected by T cell numbers, expression of memory markers, IL-2 production, proliferation, and differentiation into Th1/Th2 phenotypes. Immunization induced comparable levels of IgG2a and IgG1 antibodies. Chimeric mice, generated by transfer of CrkL(-/-) fetal liver cells into irradiated RAG2(-/-) recipients, also showed normal T cell function, arguing against selection via partial embryonic lethality. Our results indicate that CrkL is not absolutely required for T cell development or function, and argue against it being an essential component of a negative regulatory pathway in TCR signaling.

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Adaptor Proteins, Signal TransducingAnimalsAntibody FormationCell DifferentiationDNA-Binding ProteinsInterferon-gammaLymphocyte ActivationMiceMice, Inbred C57BLNuclear ProteinsT-LymphocytesTh1 CellsTh2 CellsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Amy C Peterson, Reinhard E Marks, Patrick E Fields, Akira Imamoto, Thomas F Gajewski. 2003. T cell development and function in CrkL-deficient mice.. https://doi.org/10.1002/eji.200324294

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