title: The requirements for natural Th17 cell development are distinct from those of conventional Th17 cells.
abstract: CD4(+) T helper 17 (Th17) cells play a critical role in the adaptive immune response against extracellular pathogens. Most studies to date have focused on understanding the differentiation of Th17 cells from naive CD4(+) T cells in peripheral effector sites. However, Th17 cells are present in the thymus. In this study, we demonstrate that a population of Th17 cells, natural Th17 cells (nTh17 cells), which acquire effector function during development in the thymus before peripheral antigen exposure, shows preferential usage of T cell receptor Vβ3. nTh17 cells are dependent on major histocompatibility complex (MHC) class II for thymic selection, yet unlike conventional CD4(+) T cells, MHC class II expression on thymic cortical epithelium is not sufficient for their development, rather expression on medullary epithelium is necessary. Differential signaling requirements for IL-17 priming further distinguish nTh17 from conventional Th17 cells. Collectively, our findings define a Th17 population, poised to rapidly produce cytokines, that is developmentally distinct from conventional Th17 cells and that potentially functions at the interface of innate and adaptive immunity.
authors.affiliation: Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jiyeon S
authors.initials: JS
authors.lastname: Kim
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Smith-Garvin
authors.forename: Gary A
authors.initials: GA
authors.lastname: Koretzky
authors.forename: Martha S
authors.initials: MS
authors.lastname: Jordan
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell