UMMS Affiliation
Department of Pathology
Publication Date
2009-05-19
Document Type
Article
Subjects
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
Disciplines
Immunology and Infectious Disease
Abstract
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.
Rights and Permissions
Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.
DOI of Published Version
10.1073/pnas.0808459106
Source
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8308-13. Link to article on publisher's site
Journal/Book/Conference Title
Proceedings of the National Academy of Sciences of the United States of America
Related Resources
PubMed ID
19416854
Repository Citation
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.
https://escholarship.umassmed.edu/oapubs/2206