Enhanced development of CD4+ gammadelta T cells in the absence of Itk results in elevated IgE production.
The Tec kinase Itk is critical for the development of alphabeta T cells as well as differentiation of CD4(+) T cells into Th2 cells. Itk null mice have defects in the production of Th2 cytokines; however, they paradoxically have significant elevations in serum IgE. Here we show that Itk null mice have increased numbers of gammadelta T cells in the thymus and spleen. This includes elevated numbers of CD4(+) gammadelta T cell, the majority of which carry the Vgamma1.1 and Vdelta6.2/3 gammadelta T-cell receptor with a distinct phenotype. The development of these CD4(+) gammadelta T cells is T cell intrinsic, independent of either major histocompatibility complex class I or class II, and is favored during development in the absence of Itk. Itk null CD4(+) gammadelta T cells secrete significant amounts of Th2 cytokines and can induce the secretion of IgE by wild-type B cells. Our data indicate that Itk plays important role in regulating gammadelta T-cell development and function. In addition, our data indicate that the elevated IgE observed in Itk-deficient mice is due in part to the enhanced development of CD4(+) gammadelta T cells in the absence of Itk.
Qi
Qian
Q
Center for Molecular Immunology & Infectious Disease, Department of Veterinary & Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA. avery@psu.edu
Xia
Mingcan
M
Hu
Jianfang
J
Hicks
Elizabeth
E
Iyer
Archana
A
Xiong
Na
N
August
Avery
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D049109:Cell Proliferation; D016207:Cytokines; D007073:Immunoglobulin E / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells; D013950:Thymus Gland / Q000166:cytology
D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase