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.