Stimulation of T-Cell activation by CXCL12/stromal cell derived factor-1 involves a G-protein mediated signaling pathway

Cell Immunol. 2001 Dec 15;214(2):145-54. doi: 10.1006/cimm.2001.1890.

Abstract

Recently we found that CXCL12/SDF-1 is a costimulator of peripheral CD4+ T cells. In this study, we report that CXCL12 alone induced expression of activation markers by peripheral CD4+ memory T cells and costimulated activation marker expression by anti-CD3 stimulated peripheral CD4+ naive and CD4+ memory T cells as well as by peripheral CD8+ T cells. The stimulation by CXCL12 was inhibited by Pertussis Toxin (PTX), but not by anti-CD25 mAb. CXCL12 also induced enhancement of IL-2 production and proliferation by anti-CD3 stimulated CD4+ memory T cells, but not by CD4+ naive T cells. PTX inhibited the enhancement of IL-2 production and proliferation, whereas anti-CD25 mAb inhibited proliferation, but not IL-2 production. Thus, CXCL12 upregulated T-cell activation, and a G-coupled protein mediated signaling pathway was necessary for stimulation of T cells by CXCL12.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Protein alpha Subunit, Gi2
  • GTP-Binding Protein alpha Subunits, Gi-Go / antagonists & inhibitors
  • GTP-Binding Protein alpha Subunits, Gi-Go / physiology*
  • Humans
  • Immunologic Memory
  • Interleukin-2 / biosynthesis
  • Lectins, C-Type
  • Lymphocyte Activation / drug effects*
  • MAP Kinase Kinase 1
  • MAP Kinase Signaling System / drug effects
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Pertussis Toxin
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / physiology*
  • Signal Transduction / drug effects*
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Enzyme Inhibitors
  • Interleukin-2
  • Lectins, C-Type
  • Proto-Oncogene Proteins
  • Virulence Factors, Bordetella
  • Pertussis Toxin
  • Protein-Serine-Threonine Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • GNAI2 protein, human
  • GTP-Binding Protein alpha Subunit, Gi2
  • GTP-Binding Protein alpha Subunits, Gi-Go