title: GATA-3 regulates the homeostasis and activation of CD8+ T cells.
abstract: GATA-3, a C2C2-type zinc finger transcription factor, regulates many steps of T cell development and differentiation. It is also required for optimal production of type 2 cytokines by CD8(+) T cells. However, its role in the development and function of this subset of T cells is still poorly characterized. In this paper, we report that GATA-3 is required for MHC-mediated positive selection and final maturation of CD8 single-positive thymocytes. Deficiency of GATA-3 mediated by a CD4cre transgene led to age-dependent lymphadenopathy partly because of abnormal expansion of CD8(+) T cells driven by a cell-extrinsic mechanism. Paradoxically, GATA-3-deficient CD8(+) T cells were hyporesponsive to Ag stimulation due to a defect in the maintenance/progression, but not initiation, of activation signals. More importantly, GATA-3-deficient CD8(+) T cells were less efficient in killing Ag-bearing tumor cells in vivo. Taken together, our data further expand the role of GATA-3 in T cells.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Tai
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Pai
authors.forename: I-Cheng
authors.initials: IC
authors.lastname: Ho
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse