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

FASEB J. 2003 Aug;17(11):1567-9. doi: 10.1096/fj.02-1139fje. Epub 2003 Jun 17.

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-1alpha, 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 (approximately 1 microg/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-1alpha (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.

Publication types

  • Retracted Publication

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • Cell Adhesion*
  • Cells, Cultured
  • Chaperonin 60 / pharmacology*
  • Chemotaxis, Leukocyte / drug effects
  • Cricetinae
  • Fibronectins
  • Humans
  • Integrin beta1 / metabolism
  • Lymphocyte Activation
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Models, Immunological
  • Receptors, CCR7
  • Receptors, CXCR4 / metabolism
  • Receptors, Cell Surface / metabolism*
  • Receptors, Chemokine / metabolism*
  • Signal Transduction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Substances

  • CCR7 protein, human
  • Ccr7 protein, mouse
  • Chaperonin 60
  • Fibronectins
  • Integrin beta1
  • Membrane Glycoproteins
  • Receptors, CCR7
  • Receptors, CXCR4
  • Receptors, Cell Surface
  • Receptors, Chemokine
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors