TLR2 engagement on memory CD8(+) T cells improves their cytokine-mediated proliferation and IFN-gamma secretion in the absence of Ag.
Persistence of memory CD8(+) T cells is known to be largely controlled by common gamma chain cytokines, such as IL-2, IL-7 and IL-15. However, other molecules may be involved in this phenomenon. We show here that TLR2(-/-) mice have a decreased frequency of memory phenotype CD8(+) T cells when compared with WT mice. This prompted us to investigate the role of TLR2 in the homeostasis of memory CD8(+) T cells. We describe here a new TLR2-dependent mechanism which, in the absence of specific antigen, directly controls memory CD8(+) T-cell proliferation and IFN-gamma secretion. We demonstrate that TLR2 engagement on memory CD8(+) T cells increases their proliferation and expansion induced by IL-7 both in vitro and in vivo. We also show that TLR2 ligands act in synergy with IL-2 to induce IFN-gamma secretion in vitro. Both conclusions are obtained with spontaneously arising memory phenotype and antigen-specific memory CD8(+) T cells. Altogether, our data support the idea that continuous TLR2 signaling in response to microbial stimuli or endogenous danger signals might directly contribute to the maintenance of the diversity memory CD8(+) T cells in the organism.
Cottalorda
Anne
A
Université de Lyon, Lyon, France.
Mercier
Blandine C
BC
Mbitikon-Kobo
Florentin M
FM
Arpin
Christophe
C
Teoh
Denise Y L
DY
McMichael
Andrew
A
Marvel
Jacqueline
J
Bonnefoy-Bérard
Nathalie
N
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology*; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D055666:Lipopeptides / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000502:physiology*
D000941:Antigens; D016207:Cytokines; D019409:Interleukin-15; D020382:Interleukin-18; D007376:Interleukin-2; D015851:Interleukin-7; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D018664:Interleukin-12; D007371:Interferon-gamma