TY - JOUR
T1 - Toll-dependent control mechanisms of CD4 T cell activation
AU - Pasare, Chandrashekhar
AU - Medzhitov, Ruslan
N1 - Funding Information:
We thank Dr. Shizuo Akira for MyD88KO mice, Dr. Jason Cyster for CCL-19Fc reagent, Dr. Alexander Rudensky for discussions, and Arun Unni for critically reading the manuscript. This research was supported by a grant from the National Institute of Health (AI 05502). R.M. is an assistant investigator of the Howard Hughes Medical Institute.
PY - 2004/11
Y1 - 2004/11
N2 - Toll-like receptors (TLRs) detect microbial infection and play an essential role in the induction of innate and adaptive immune responses. The mechanisms of TLR-mediated control of adaptive immunity are not yet fully understood. Induction of dendritic cell (DC) maturation is essential for activation of naive T cells. Here, we demonstrate that TLR-induced DC maturation and migration to the lymph nodes, in the absence of TLR-induced inflammatory cytokines, are not sufficient for T cell activation in vivo. We show that transient depletion of regulatory T (Tr) cells recovers the primary CD4 T cells response in MyD88-deficient mice, demonstrating that a major mechanism of TLR-mediated activation of T cell responses is the blocking of suppression by regulatory T cells. In addition we show that a TLR-induced signal(s) is required for memory CD4 T cell differentiation, but not for activation of memory T cells.
AB - Toll-like receptors (TLRs) detect microbial infection and play an essential role in the induction of innate and adaptive immune responses. The mechanisms of TLR-mediated control of adaptive immunity are not yet fully understood. Induction of dendritic cell (DC) maturation is essential for activation of naive T cells. Here, we demonstrate that TLR-induced DC maturation and migration to the lymph nodes, in the absence of TLR-induced inflammatory cytokines, are not sufficient for T cell activation in vivo. We show that transient depletion of regulatory T (Tr) cells recovers the primary CD4 T cells response in MyD88-deficient mice, demonstrating that a major mechanism of TLR-mediated activation of T cell responses is the blocking of suppression by regulatory T cells. In addition we show that a TLR-induced signal(s) is required for memory CD4 T cell differentiation, but not for activation of memory T cells.
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U2 - 10.1016/j.immuni.2004.10.006
DO - 10.1016/j.immuni.2004.10.006
M3 - Article
C2 - 15539158
AN - SCOPUS:8444245925
SN - 1074-7613
VL - 21
SP - 733
EP - 741
JO - Immunity
JF - Immunity
IS - 5
ER -