title: Antigen-driven effector CD8 T cell function regulated by T-bet.
abstract: Type 1 immunity relies on the differentiation of two major subsets of T lymphocytes, the CD4+ T helper (Th) cell and the CD8+ cytotoxic T cell, that direct inflammatory and cytotoxic responses essential for the destruction of intracellular and extracellular pathogens. In contrast to CD4 cells, little is known about transcription factors that control the transition from the CD8 naïve to effector cell stage. Here, we report that the transcription factor T-bet, known to regulate Th cell differentiation, also controls the generation of the CD8+ cytotoxic effector cell. Antigen-driven generation of effector CD8+ cells was impaired in OT-I T cell receptor transgenic mice lacking T-bet, resulting in diminished cytotoxicity and a marked shift in cytokine secretion profiles. Furthermore, mice lacking T-bet responded poorly to infection with lymphocytic choriomeningitis virus. T-bet is a key player in the generation of type 1 immunity, in both Th and T cytotoxic cells.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Sullivan
authors.forename: Amy
authors.initials: A
authors.lastname: Juedes
authors.forename: Susanne J
authors.initials: SJ
authors.lastname: Szabo
authors.forename: Matthias
authors.initials: M
authors.lastname: von Herrath
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003433:Crosses, Genetic; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020825:T-Box Domain Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors