THE CD69 ACTIVATION PATHWAY IN RHEUMATOID-ARTHRITIS SYNOVIAL-FLUID T-CELLS

Objective, To study the CD69 activation pathway in synovial fluid (SF) T lymphocytes from patients with rheumatoid arthritis (RA), Methods, Peripheral blood mononuclear cells (PBMC) or SF mononuclear cells (SFM C) were used in proliferation assays with anti-CD69, anti-CD28, anti-C D3, phorbol myristate acetate (PMA), and/or recombinant interleukin-2 (IL-2), CD69+, CD69-, and resting SF T cells were also proliferated, C D25 expression and production of IL-2 after CD69 activation were asses sed by flow cytometry and in a bioassay with the IL-2-dependent cell l ine CTLL-2, Results, RA SFMC did not proliferate either in the presenc e of anti-CD69 monoclonal antibodies alone or with concomitant PMA act ivation, when compared with paired or control PBMC, Similar low prolif erative responses via the CD3 or CD28 pathway with PMA were observed, This defective proliferation of RA SFMC after stimulation through the CD69 molecule was explained in part by a failure to express CD25 and t o produce IL-2, SF CD69- T cells and resting SF T cells had higher rat es of proliferation through the alternative costimulatory pathway CD28 than did SF CD69+ T cells or freshly isolated SF T cells, Conclusion. Freshly isolated SF T cells present a profound state of hyporesponsiv eness through the CD69 and CD28 costimulatory pathways, This state app ears to be dependent on the activation status of SF T cells, since CD6 9- and resting SF T cells showed recovery of the ability to proliferat e through the CD28 activation pathway.