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      Expression of activation-induced, T cell-derived, and chemokine-related cytokine/lymphotactin and its functional role in rheumatoid arthritis.

      Arthritis and Rheumatism

      Adult, Aged, Aged, 80 and over, Arthritis, Rheumatoid, immunology, CD4-Positive T-Lymphocytes, cytology, metabolism, CD8-Positive T-Lymphocytes, Cells, Cultured, Chemokines, C, Female, Gene Expression, Humans, Lymphocyte Activation, drug effects, Lymphokines, genetics, pharmacology, Male, Middle Aged, Osteoarthritis, Phenotype, RNA, Messenger, analysis, Sialoglycoproteins, Synovial Fluid, Synovial Membrane

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          To evaluate the possible role of activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin (Lptn) in the pathogenesis of rheumatoid arthritis (RA). ATAC/Lptn levels in serum and synovial fluid samples were measured by sandwich enzyme-linked immunosorbent assay. Expression of messenger RNA for ATAC/Lptn in synovial tissues was analyzed by reverse transcription-polymerase chain reaction (PCR) and by in situ hybridization, and was quantitated by real-time PCR. The phenotype of peripheral blood mononuclear cells (PBMCs) expressing ATAC/Lptn was analyzed by intracellular cytokine staining and flow cytometry. Levels of ATAC/Lptn were similar in sera and synovial fluids from RA patients (n = 20) and osteoarthritis controls (n = 15). In phorbol myristate acetate/ionomycin-stimulated PBMCs, ATAC/Lptn expression was detected in CD8+ T cells and in a significantly increased proportion of CD4+,CD28- T cells from RA patients as compared with healthy controls. In synovial tissues, ATAC/Lptn was predominantly localized in CD3+ T cells in the sublining layer. Lymphocytes, synovial macrophages, and, unexpectedly, fibroblast-like synoviocytes (FLS) were identified as major target cells for ATAC/Lptn in RA synovium, as determined by analysis of the ATAC/Lptn receptor XCR1. In vitro, ATAC/Lptn stimulation of FLS resulted in a marked down-regulation of matrix metalloproteinase 2 production. These data indicate that in RA synovium, ATAC/Lptn is mainly produced by T cells. Considering its function as a lymphocyte-specific chemoattractant, ATAC/Lptn might be a key modulator for T cell trafficking in the pathogenesis of RA. In addition, functional studies suggest that ATAC/Lptn may exert additional immunomodulatory effects in RA.

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