Department of Pathology
Animals; B-Lymphocytes; Cell Lineage; Cytokines; Immunoglobulin Class Switching; Immunoglobulin E; Lymphocyte Activation; Mice; Mice, Knockout; Natural Killer T-Cells; Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell, alpha-beta; *Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes; Th2 Cells
Immunology and Infectious Disease
In conventional alphabeta T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the T cell receptor (TCR). Itk also regulates alphabeta T cell development, lineage commitment, and effector function. A well established feature of Itk(-/-) mice is their inability to generate T helper type 2 (Th2) responses that produce IL-4, IL-5, and IL-13; yet these mice have spontaneously elevated levels of serum IgE and increased numbers of germinal center B cells. Here we show that the source of this phenotype is gammadelta T cells, as normal IgE levels are observed in Itk(-/-)Tcrd(-/-) mice. When stimulated through the gammadelta TCR, Itk(-/-) gammadelta T cells produce high levels of Th2 cytokines, but diminished IFNgamma. In addition, activated Itk(-/-) gammadelta T cells up-regulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Furthermore, we find that gammadelta T cells numbers are increased in Itk(-/-) mice, most notably the Vgamma1.1(+)Vdelta6.3(+) subset that represents the dominant population of gammadelta NKT cells. Itk(-/-) gammadelta NKT cells also have increased expression of PLZF, a transcription factor required for alphabeta NKT cells, indicating a common molecular program between alphabeta and gammadelta NKT cell lineages. Together, these data indicate that Itk signaling regulates gammadelta T cell lineage development and effector function and is required to control IgE production in vivo.
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DOI of Published Version
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8308-13. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Felices, Martin; Yin, Catherine C.; Kosaka, Yoko; Kang, Joonsoo; and Berg, Leslie J., "Tec kinase Itk in gammadeltaT cells is pivotal for controlling IgE production in vivo" (2009). Open Access Articles. 2206.