T-cell receptor activation of human CD4(+) T cells shifts the innate TLR response from CXCL8(hi) IFN-γ(null) to CXCL8(lo) IFN-γ(hi).

Toll-like receptors (TLRs) play a major part in providing innate immunity against pathogenic microorganisms. Recent studies show that these receptors are also expressed on T cells, which are the sentinels of adaptive immunity. Here, we have investigated the regulatory role of the T-cell receptor in the functioning of these innate receptors in T cells. We show that freshly isolated human CD4(+) T cells readily secrete the neutrophil chemoattractant CXCL8 upon activation with the TLR ligands Pam3CSK and flagellin. In contrast, TCR-activated cells secrete considerably less CXCL8 but start producing IFN-γ upon stimulation with TLR agonists in the absence of concomitant TCR engagement. These T cells show increased activation of p38 and JNK MAP-kinases in response to TLR stimulation, and inhibition of p38 abrogates TLR-induced IFN-γ secretion. The shifting of the T-cell innate immune response from CXCL8(hi) IFN-γ(null) in freshly isolated to CXCL8(lo) IFN-γ(hi) in activated T cells is also observed in response to endogenous innate stimulus, IL-1. These results suggest that the innate immune response of human CD4(+) T cells switches from a proinflammatory to an effector type following activation of these cells through the antigen receptor.