Mutation of Tec family kinases alters T helper cell differentiation

Edward M. Schaeffer, George S. Yap, Carol M. Lewis, Michael J. Czar, Daniel W. McVicar, Allen W. Cheever, Alan Sher, Pamela L. Schwartzberg

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

The Tec kinases Rlk and Itk are critical for full T cell receptor (TCR)-induced activation of phospholipase C-γ and mitogen-activated protein kinase. We show here that the mutation of Rlk and Itk impaired activation of the transcription factors NFAT and AP-I and production of both T helper type I (THI) and TH2 cytokines. Consistent with these biochemical defects, Itk-/- mice did not generate effective TH2 responses when challenged with Schistosoma mansoni eggs. Paradoxically, the more severely impaired Rlk-/-Itk-/- mice were able to mount a TH2 response and produced TH2 cytokines in response to this challenge. In addition, Rlk-/-Itk-/- cells showed impaired TCR-induced repression of the TH2-inducing transcription factor GATA-3, suggesting a potential mechanism for TH2 development in these hyporesponsive cells. Thus, mutations that affect Tec kinases lead to complex alterations in CD4+TH cell differentiation.

Original languageEnglish (US)
Pages (from-to)1183-1188
Number of pages6
JournalNature Immunology
Volume2
Issue number12
DOIs
StatePublished - Dec 22 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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