title: Development and function of innate polyclonal TCRalphabeta+ CD8+ thymocytes.
abstract: Innate CD8 T cells are found in mutant mouse models, but whether they are produced in a normal thymus remains controversial. Using the RAG2p-GFP mouse model, we found that ∼10% of TCRαβ(+) CD4(-)CD8(+) thymocytes were innate polyclonal T cells (GFP(+)CD44(hi)). Relative to conventional T cells, innate CD8 thymocytes displayed increased cell surface amounts of B7-H1, CD2, CD5, CD38, IL-2Rβ, and IL-4Rα and downmodulation of TCRβ. Moreover, they overexpressed several transcripts, including T-bet, Id3, Klf2, and, most of all, Eomes. Innate CD8 thymocytes were positively selected, mainly by nonhematopoietic MHCIa(+) cells. They rapidly produced high levels of IFN-γ upon stimulation and readily proliferated in response to IL-2 and IL-4. Furthermore, low numbers of innate CD8 thymocytes were sufficient to help conventional CD8 T cells expand and secrete cytokine following Ag recognition. This helper effect depended on CD44-mediated interactions between innate and conventional CD8 T cells. We concluded that innate TCRαβ(+) CD8 T cells represent a sizeable proportion of normal thymocytes whose development and function differ in many ways from those of conventional CD8 T cells.
authors.affiliation: Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3C 3J7, Canada.
authors.forename: Moutih
authors.initials: M
authors.lastname: Rafei
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Hardy
authors.forename: Patrick
authors.initials: P
authors.lastname: Williams
authors.forename: Juan Ruiz
authors.initials: JR
authors.lastname: Vanegas
authors.forename: Kathy-Ann
authors.initials: KA
authors.lastname: Forner
authors.forename: Gaël
authors.initials: G
authors.lastname: Dulude
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labrecque
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
authors.forename: Claude
authors.initials: C
authors.lastname: Perreault
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta