Stimulation of T-Cell activation by CXCL12/stromal cell derived factor-1 involves a G-protein mediated signaling pathway.
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.
Nanki
T
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National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892-1820, USA.
Lipsky
P E
PE
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D037342:Pertussis Toxin; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004791:Enzyme Inhibitors; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007376:Interleukin-2; D037181:Lectins, C-Type; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D037342:Pertussis Toxin; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D010566:Virulence Factors, Bordetella; D000099192:CD69 Antigens; C515255:CXCL12 protein, human; C482125:MAP2K1 protein, human; C498015:GNAI2 protein, human