Cutting edge: Itk-dependent signals required for CD4+ T cells to exert, but not gain, Th2 effector function.
The TCR signals for the release of CD4 effector function are poorly understood. Itk plays an essential role in Th2, but not Th1, responses. However, when Itk is required during Th2 development is unclear. We followed the fate of Itk-deficient T cells during Th2 development in vitro and in vivo using an IL-4/GFP reporter. Surprisingly, a similar frequency of itk(-/-) CD4(+) cells differentiated and committed to the Th2 lineage as wild-type cells. However, Itk-deficient Th2 cells failed to exert effector function upon TCR triggering. Loss of function was marked by defective transcriptional enhancement of Th2 cytokines and GATA3. IL-4 production in itk(-/-) Th2s could be rescued by the expression of kinase-active Itk. Thus, Itk is necessary for the release, but not gain, of Th2 function. We suggest that the liberation of effector function is tightly controlled through qualitative changes in TCR signals, facilitating postdifferentiation regulation of cytokine responses.
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, NY 14642, USA.
Byron B
BB
Au-Yeung
Shoshana D
SD
Katzman
Deborah J
DJ
Fowell
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
D016207:Cytokines; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase