T cell activation by TLRs: a role for TLRs in the adaptive immune response.
Toll-like receptor (TLR) activation is primarily thought to affect antigen-presenting cells (APCs) by inducing an innate immune response that can subsequently activate the adaptive immune system. However, there are increasing data that demonstrate expression and activation of TLRs on T cells, thus providing evidence for a direct role for TLRs in the activation of an adaptive immune response. A study recently demonstrated that Pam3CSK {N-palmitoyl-S-[2,3-bis(palmitoloxy)-(2RS)-propyl]-Cys-Ser-Lys(4)}, a TLR2 agonist lipopeptide, activates T helper 1 (T(H)1) cells and induces interferon-gamma (IFN-gamma) production, even in the absence of TLR1, which differs from its mechanism of activation of APCs. Moreover, whereas Pam3CSK-stimulated IFN-gamma production by T(H)1 cells is ablated in the absence of both myeloid differentiation marker 88 (MyD88), an adaptor protein in the TLR pathway, and interleukin-1 receptor (IL-1R)-associated kinase-4 (IRAK4), the mitogen-activated protein kinases p38 and c-Jun N-terminal kinase (JNK) are still phosphorylated. These data suggest that TLR2 activation of T(H)1 cells occurs through a mechanism different from that described for APCs and provides further evidence of direct TLR activation of the adaptive immune system.
MacLeod
Heather
H
Department of Microbiology, Immunology Training Program, Evans Biomedical Research Center, Boston University School of Medicine, Boston, MA 02118, USA.
Wetzler
Lee M
LM
D000222:Adaptation, Physiological; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D007109:Immunity / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000502:physiology*