Toll-dependent control mechanisms of CD4 T cell activation.
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.
Pasare
Chandrashekhar
C
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Medzhitov
Ruslan
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000502:physiology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors