title: TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation.
abstract: TLR have a crucial role in the detection of microbial infection in mammals. Until recently, most investigations on TLR have focused on cells of the innate immune system and on the role of TLR in the initiation of antigen-specific responses following recognition of microbial products by APC. Here, we report that murine T cells express TLR1, TLR2, TLR6, TLR7 and TLR9 mRNA. Using CD8 T cells from F5 TCR-transgenic mice, we demonstrate that the lipopeptide Pam(3)CysSK(4) (Pam), a synthetic analog of bacterial and mycoplasmal lipoproteins that recognizes TLR1/2 complex, costimulates antigen-activated T cells. Costimulation with Pam permits an increased cell proliferation and survival associated with a sustained CD25 expression and an enhanced expression of Bcl-xL anti-apoptotic protein. In addition, we show that costimulation with Pam up-regulates IFN-gamma production but also granzyme B secretion and cytotoxic activity of antigen-activated T cells, indicating that TLR2 engagement enhances the major effector functions of CD8 T cells. Finally, we demonstrate that TLR2 engagement on T cells lowers the activation threshold for costimulatory signals delivered by APC.
authors.affiliation: Laboratory of Homéostasie Lymphocytaire, INSERM, U503, IFR Biosciences Lyon-Gerland, Université Claude Bernard Lyon I, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cottalorda
authors.forename: Claire
authors.initials: C
authors.lastname: Verschelde
authors.forename: Antoine
authors.initials: A
authors.lastname: Marçais
authors.forename: Martine
authors.initials: M
authors.lastname: Tomkowiak
authors.forename: Philippe
authors.initials: P
authors.lastname: Musette
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marvel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonnefoy-Berard
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D051194:Toll-Like Receptor 1 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D000941:Antigens; D008024:Ligands; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2