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 M, Yin CC, Kosaka Y, Kang J, Berg LJ. (2009). Tec kinase Itk in gammadeltaT cells is pivotal for controlling IgE production in vivo. Open Access Articles. https://doi.org/10.1073/pnas.0808459106. Retrieved from https://escholarship.umassmed.edu/oapubs/2206