Cutting edge: stromal cell-derived factor-1 is a costimulator for CD4+ T cell activation.
Stromal cell-derived factor (SDF)-1 is a chemoattractant for T cells, precursor B cells, monocytes, and neutrophils. SDF-1alpha was also found to up-regulate expression of early activation markers (CD69, CD25, and CD154) by anti-CD3-activated CD4+ T cells. In addition, SDF-1alpha costimulated proliferation of CD4+ T cells and production of IL-2, IFN-gamma, IL-4, and IL-10. Stimulation with SDF-1alpha alone did not induce activation marker expression, proliferation, or cytokine production by the CD4+ T cells. SDF-1alpha-mediated costimulation was blocked by anti-CXC chemokine receptor-4 mAb. RANTES also increased activation marker expression by anti-CD3-stimulated peripheral CD4+ T cells, but less effectively than SDF-1alpha did, and did not up-regulate IL-2 production and proliferation. These results indicate that SDF-1 and CXC chemokine receptor-4 interactions not only play a role in T cell migration but also provide potent costimulatory signals to Ag-stimulated T cells.
Nanki
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Department of Internal Medicine, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Lipsky
P E
PE
D000276:Adjuvants, Immunologic / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D004357:Drug Synergism; D006801:Humans; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D016853:Muromonab-CD3 / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D017154:Stromal Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D023201:CD40 Ligand; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D019718:Receptors, CXCR4; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens; C515255:CXCL12 protein, human