Abstract
Rheumatoid arthritis (RA) is characterized by the accumulation of CD4(+) memory T cells in the inflamed synovium. To address the mechanism, we analyzed chemokine receptor expression and found that the frequency of CXC chemokine receptor (CXCR)4 expressing synovial tissue CD4(+) memory T cells was significantly elevated. CXCR4 expression could be enhanced by IL-15, whereas stromal cell-derived factor (SDF)-1, the ligand of CXCR4, was expressed in the RA synovium and could be increased by CD40 stimulation. SDF-1 stimulated migration of rheumatoid synovial T cells and also inhibited activation-induced apoptosis of T cells. These results indicate that SDF-1-CXCR4 interactions play important roles in CD4(+) memory T cell accumulation in the RA synovium, and emphasize the role of stromal cells in regulating rheumatoid inflammation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / physiology
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Antibodies, Monoclonal / pharmacology
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Apoptosis / immunology
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Arthritis, Rheumatoid / blood
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / pathology
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CD4 Antigens / biosynthesis
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CD4 Antigens / blood
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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CD40 Antigens / immunology
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Cell Communication / immunology
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Cell Movement / immunology*
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Chemokine CXCL12
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Chemokines, CXC / metabolism
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Chemokines, CXC / physiology*
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Fibroblasts / immunology
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Humans
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Interleukin-15 / pharmacology
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Leukocyte Common Antigens / biosynthesis
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Leukocyte Common Antigens / blood
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Lymphocyte Activation / immunology
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Osteoarthritis / immunology
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Osteoarthritis / metabolism
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Osteoarthritis / pathology
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RNA, Messenger / biosynthesis
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Receptors, CXCR4 / biosynthesis
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Receptors, CXCR4 / genetics
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Receptors, CXCR4 / metabolism
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Receptors, CXCR4 / physiology*
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Stromal Cells / immunology
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Synovial Membrane / immunology*
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Synovial Membrane / metabolism
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Synovial Membrane / pathology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / pathology
Substances
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Adjuvants, Immunologic
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Antibodies, Monoclonal
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CD4 Antigens
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CD40 Antigens
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CXCL12 protein, human
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Chemokine CXCL12
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Chemokines, CXC
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Interleukin-15
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RNA, Messenger
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Receptors, CXCR4
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Leukocyte Common Antigens