What determines Th2 differentiation, in vitro and in vivo?
We have known since 1991 how to induce naive CD4 T cells to differentiate in vitro into Th2 cells and, over the ensuing years, a comprehensive picture of the molecules involved in this important process has emerged. GATA3 and STAT5 are both essential for in vitro differentiation, stimulating naive cells through a process involving induction, which is T-cell receptor (TCR) dependent but interleukin (IL)-4 independent, and commitment, which is IL-4 dependent. Th2 differentiation in vivo appears more complex. GATA3 and probably STAT5 are required in vivo but, at least for certain helminth infections, the IL-4/IL-4Ra/STAT6 pathway is dispensable. The role of thymic stromal lymphopoietin and of low TCR signal strength and the participation of basophils in establishing a Th2-baising in vivo environment have achieved considerable attention. Here I discuss the major players in Th2 differentiation particularly as they may exert their effects in vivo.
Paul
William E
WE
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. wpaul@niaid.nih.gov
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000276:immunology; D006373:Helminthiasis / Q000276:immunology; D006376:Helminths / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D019948:Receptors, Interleukin-4 / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508598:IL4 protein, human; D011948:Receptors, Antigen, T-Cell; D019948:Receptors, Interleukin-4; D050799:STAT5 Transcription Factor; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin