HIGH AVIDITY STATE OF LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 ON RHEUMATOID SYNOVIAL-FLUID T-LYMPHOCYTES

The integrin LFA-1 (CD11a/CD18) is a cell surface adhesion molecule re quired for leukocyte extravasation and subsequent immune and inflammat ory responses. Rapid transition between nonadherent and adherent state s of LFA-1 is of key importance to Ag-specific recognition of T lympho cytes. In this paper, LFA-1-mediated adhesiveness of peripheral blood (PB) and synovial fluid (SF) T lymphocytes to affinity-purified ICAM-1 -coated plates was studied in patients with rheumatoid arthritis (RA) and in patients with non-RA panels, including osteoarthritis, ankylosi ng spondylitis, erythema nodosum, pseudogout, and pustulosis. LFA-1-me diated adhesiveness of SF T lymphocytes was not observed in any of the 10 non-RA patients studied, although cross-linking of the TCR on lymp hocytes from these patients rapidly converted LFA-1 to an adhesive sta te. In contrast, SF T lymphocytes from 10 of 12 RA patients exhibited LFA-1-mediated adhesiveness without a requirement for cross-linking of the TCR. No difference was seen in the cell surface density of LFA-1 between non-RA and RA T lymphocytes, suggesting that the difference in adhesiveness was due to a high avidity state of LFA-1 on SF T lymphoc ytes in RA. Furthermore, exposure of PB T lymphocytes, which showed a low avidity state of LFA-1, to whole SF from RA patients that was depl eted of T lymphocytes could induce a high avidity state of LFA-1 in vi tro. Cellfree SF from RA patients also could stimulate adhesiveness, a lthough to a lesser extent. These data suggest the existence of a LFA- 1-activating environment that is selectively found in SF from RA patie nts.