TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation.
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.
Cottalorda
Anne
A
Laboratory of Homéostasie Lymphocytaire, INSERM, U503, IFR Biosciences Lyon-Gerland, Université Claude Bernard Lyon I, Lyon, France.
Verschelde
Claire
C
Marçais
Antoine
A
Tomkowiak
Martine
M
Musette
Philippe
P
Uematsu
Satoshi
S
Akira
Shizuo
S
Marvel
Jacqueline
J
Bonnefoy-Berard
Nathalie
N
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
D000941:Antigens; D008024:Ligands; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2