Mutation of Tec family kinase alters T helper cell differentiation

Citation
Em. Schaeffer et al., Mutation of Tec family kinase alters T helper cell differentiation, NAT IMMUNOL, 2(12), 2001, pp. 1183-1188
Citations number
45
Categorie Soggetti
Immunology
Journal title
NATURE IMMUNOLOGY
ISSN journal
15292908 → ACNP
Volume
2
Issue
12
Year of publication
2001
Pages
1183 - 1188
Database
ISI
SICI code
1529-2908(200112)2:12<1183:MOTFKA>2.0.ZU;2-F
Abstract
The Tec kinases RIk and Itk are critical for full T cell receptor (TCR)-ind uced activation of phospholipase C-gamma and mitogen-activated protein kina se. We show here that the mutation of RIk and Itk impaired activation of th e transcription factors NFAT and AP-1 and production of both T helper type I (T(H)1) and T(H)2 cytokines. Consistent with these biochemical defects, I tk(-/-) mice did not generate effective T(H)2 responses when challenged wit h Schistosoma mansoni eggs. Paradoxically, the more severely impaired RIk(- /-)Itk(-/-) mice were able to mount a T(H)2 response and produced T(H)2 cyt okines in response to this challenge. In addition, RIk(-/-)Itk(-/-) cells s howed impaired TCR-induced repression of the T(H)2-inducing transcription f actor GATA-3, suggesting a potential mechanism for T(H)2 development in the se hyporesponsive cells. Thus, mutations that affect Tec kinases lead to co mplex alterations in CD4(+)T(H) cell differentiation.