PMID- 10332965 OWN - NLM STAT- MEDLINE DCOM- 19990630 LR - 20171116 IS - 0315-162X (Print) IS - 0315-162X (Linking) VI - 26 IP - 5 DP - 1999 May TI - Ligation of CD40 induced tumor necrosis factor-alpha in rheumatoid arthritis: a novel mechanism of activation of synoviocytes. PG - 1035-43 AB - OBJECTIVE: To determine the immunopathological significance of CD40/CD40 ligand (CD40L) interaction in rheumatoid arthritis (RA). METHODS: The expression of CD40 ligand (CD40L) in synovial tissues (ST) from patients with RA was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) was measured by ELISA. Expression of CD40 on ST cells was quantified by anti-CD40 monoclonal antibodies and 125I labelled anti-mouse IgG. RESULTS: Immunohistochemistry showed CD40L+ T cells in RA ST. Ligation of CD40 on RA ST cells significantly increased the production of TNF-alpha in a dose dependent fashion. Adherent, but not non-adherent, fraction of ST cells responded to ligation of CD40 to produce TNF-alpha. Interferon-gamma (IFN-gamma), interleukin 4 (IL-4), or IL-13 acted synergistically with CD40 ligation to enhance TNF-alpha production by ST cells. IL-10 exerted inhibitory effects on both CD40 ligation induced and CD40 ligation plus IFN-gamma induced TNF-alpha production by ST cells. CONCLUSION: These data indicate activated T cells participate in synovial inflammation of RA via CD40L to stimulate the production of TNF-alpha by ST cells. The effect of CD40 ligation is modulated by the presence of several cytokines, e.g., IFN-gamma, IL-4, IL-10, and IL-13. FAU - Harigai, M AU - Harigai M AD - Institute of Rheumatology, Tokyo Women's Medical University, Japan. FAU - Hara, M AU - Hara M FAU - Nakazawa, S AU - Nakazawa S FAU - Fukasawa, C AU - Fukasawa C FAU - Ohta, S AU - Ohta S FAU - Sugiura, T AU - Sugiura T FAU - Inoue, K AU - Inoue K FAU - Kashiwazaki, S AU - Kashiwazaki S LA - eng PT - Journal Article PL - Canada TA - J Rheumatol JT - The Journal of rheumatology JID - 7501984 RN - 0 (CD40 Antigens) RN - 0 (Cytokines) RN - 0 (Membrane Glycoproteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 147205-72-9 (CD40 Ligand) SB - IM MH - Arthritis, Rheumatoid/immunology/*metabolism/pathology MH - *CD40 Antigens/metabolism MH - CD40 Ligand MH - Cells, Cultured MH - Cytokines/biosynthesis/immunology MH - Humans MH - Interleukin-10/metabolism MH - Lymphocyte Activation MH - Membrane Glycoproteins/biosynthesis/*metabolism MH - Synovial Membrane/metabolism/*pathology MH - T-Lymphocytes/immunology/pathology MH - Tumor Necrosis Factor-alpha/biosynthesis/*metabolism EDAT- 1999/05/20 00:00 MHDA- 1999/05/20 00:01 CRDT- 1999/05/20 00:00 PHST- 1999/05/20 00:00 [pubmed] PHST- 1999/05/20 00:01 [medline] PHST- 1999/05/20 00:00 [entrez] PST - ppublish SO - J Rheumatol. 1999 May;26(5):1035-43.