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.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. wpaul@niaid.nih.gov
William E
WE
Paul
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