title: CD28 controls the development of innate-like CD8+ T cells by promoting the functional maturation of NKT cells.
abstract: NK T cells(NKT cells) share functional characteristics and homing properties that are distinct from conventional T cells. In this study, we investigated the contribution of CD28 in the functional development of γδ NKT and αβ NKT cells in mice. We show that CD28 promotes the thymic maturation of promyelocytic leukemia zinc finger(+) IL-4(+) NKT cells and upregulation of LFA-1 expression on NKT cells. We demonstrate that the developmental defect of γδ NKT cells in CD28-deficient mice is cell autonomous. Moreover, we show in both wild-type C57BL/6 mice and in downstream of tyrosine kinase-1 transgenic mice, a mouse model with increased numbers of γδ NKT cells, that CD28-mediated regulation of thymic IL-4(+) NKT cells promotes the differentiation of eomesodermin(+) CD44(high) innate-like CD8(+) T cells. These findings reveal a previously unappreciated mechanism by which CD28 controls NKT-cell homeostasis and the size of the innate-like CD8(+) T-cell pool.
authors.affiliation: Institut National de la Recherche Scientifique-Institut Armand-Frappier, Université du Québec, Laval, Canada.
authors.forename: Mitra
authors.initials: M
authors.lastname: Yousefi
authors.forename: Pascale
authors.initials: P
authors.lastname: Duplay
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000378:metabolism*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018106:CD28 Antigens; C491198:Eomes protein, mouse; D018960:Hyaluronan Receptors; D051741:Kruppel-Like Transcription Factors; D016169:Lymphocyte Function-Associated Antigen-1; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020825:T-Box Domain Proteins; C513267:Zbtb16 protein, mouse; D015847:Interleukin-4
keywords: CD28; Innate-like CD8 T cells; NKT cells; PLZF; Thymocyte development