Rheumatoid synovial fibroblasts are stimulated by the cellular adhesion to T cells through lymphocyte function associated antigen-1/intercellular adhesion molecule-1.
OBJECTIVE
To determine if T cells stimulate synovial fibroblasts to produce inflammatory cytokines through cellular adhesion in synovitis of rheumatoid arthritis (RA).


METHODS
Immunohistochemical staining, flow microfluorometry, adhesion assay, ELISA, and Northern blot analysis to determine production of interleukin-1beta (IL-1beta) from RA synovium and RA synovial fibroblast-like cell line.


RESULTS
We observed the following novel features of cellular adhesion of T cells to synovial fibroblasts, which suggest a role for induction of cytokine production in synovial fibroblasts: (a) CD11a (lymphocyte function associated antigen-1 alpha) positive T cells accumulated around CD54 [intercellular adhesion molecule (ICAM-1)] positive synoviocytes in active RA synovium, shown by immunohistochemical studies: (b) synovial fibroblastic cell line E11 expressed a single adhesion molecule ICAM-1, the expression of which was not affected by IL-1beta; (c) E11 adhered to phorbol myristate acetate (PMA) activated T cells within 30 min, not resting T cells, and its adhesion was completely inhibited by anti-LFA-1 monoclonal antibody (Mab); (d) pretreatment of E11 with IL-1beta did not affect the adhesion of E11 to PMA activated T cells; (e) IL-1beta production and IL-1beta mRNA transcription from E11 were induced by the addition of T cells in a cell number dependent manner and the induced production and transcription were inhibited by anti-LFA-1 Mab.


CONCLUSIONS
T cells infiltrating the synovium may play a pivotal role in the pathogenesis of RA, by inducing IL-1beta production of synovial fibroblasts by sequential events, namely, T cell-synoviocyte cellular adhesion through LFA-1/ICAM-1, signal transduction, and production of IL-1beta induced by the cellular adhesion.
Nakatsuka
K
K
First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Tanaka
Y
Y
Hubscher
S
S
Abe
M
M
Wake
A
A
Saito
K
K
Morimoto
I
I
Eto
S
S
D001172:Arthritis, Rheumatoid / Q000150:complications / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology*; D013585:Synovitis / Q000150:complications / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D013755:Tetradecanoylphorbol Acetate