title: GATA-3 controls the maintenance and proliferation of T cells downstream of TCR and cytokine signaling.
abstract: GATA-3 controls T helper type 2 (TH2) differentiation. However, whether GATA-3 regulates the function of mature T cells beyond TH2 determination remains poorly understood. We found that signaling via the T cell antigen receptor (TCR) and cytokine stimulation promoted GATA-3 expression in CD8(+) T cells, which controlled cell proliferation. Although GATA-3-deficient CD8(+) T cells were generated, their peripheral maintenance was impaired, with lower expression of the receptor for interleukin 7 (IL-7R). GATA-3-deficient T cells had defective responses to viral infection and alloantigen. The proto-oncoprotein c-Myc was a critical target of GATA-3 in promoting T cell proliferation. Our study thus demonstrates an essential role for GATA-3 in controlling the maintenance and proliferation of T cells and provides insight into immunoregulation.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Ichiro
authors.initials: I
authors.lastname: Misumi
authors.forename: Ai-Di
authors.initials: AD
authors.lastname: Gu
authors.forename: T Anthony
authors.initials: TA
authors.lastname: Curtis
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
authors.forename: Jason K
authors.initials: JK
authors.lastname: Whitmire
authors.forename: Yisong Y
authors.initials: YY
authors.lastname: Wan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050990:GATA3 Transcription Factor; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D012313:RNA