T cells respond to heat shock protein 60 via TLR2: activation of adhesion and inhibition of chemokine receptors

Abstract

Soluble 60 kDa heat shock protein (HSP60) activates macrophages via TLR4. We now report that soluble HSP60 activates T cells via the innate receptor TLR2. HSP60 activated T cell adhesion to fibronectin to a degree similar to other activators: IL‐2, SDF‐1α, and RANTES. T cell type and state of activation was important; nonactivated CD45RA + and IL‐2‐activated CD45RO + T cells responded optimally (1 h) at low concentrations (0.1–1 ng/ml), but nonactivated CD45RO + T cells required higher concentrations (∼1 εg/ml) of HSP60. T cell HSP60 signaling was inhibited specifically by monoclonal antibodies (mAb) to TLR2 but not by a mAb to TLR4. Indeed, T cells from mice with mutated TLR4 could still respond to HSP60, whereas Chinese hamster T cells with mutated TLR2 did not respond. The human T cell response to soluble HSP60 depended on phosphatidylinositol 3‐kinase and protein kinase C signaling and involved the phosphorylation of Pyk‐2. Soluble HSP60 also inhibited actin polymerization and T cell chemotaxis through extracellular matrix‐like gels toward the chemokines SDF‐1α (CXCL12) or ELC (CCL19). Exposure to HSP60 for longer times (18 h) down‐regulated chemokine receptor expression: CXCR4 and CCR7. These results suggest that soluble HSP60, through TLR2‐dependent interactions, can regulate T cell behavior in inflammation.