Antigenic specificity of rheumatoid synovial fluid lymphocytes.

The majority of rheumatoid arthritis (RA) synovial fluid lymphocytes (SFL) demonstrate markers that are suggestive of prior activation. While the mechanism(s) responsible is unknown, prior studies have suggested that certain Mycobacterium tuberculosis (MT) antigens may preferentially activate SFL in vitro. We therefore examined the ability of RA SFL to respond to purified protein derivative and an acetone-precipitable MT antigenic complex (AP-MT) and compared this with the responses by peripheral blood lymphocytes (PBL). The responses were contrasted with those elicited with tetanus toxoid (TT) and mitogenic anti-CD3. In patients with RA, the SF proliferative responses to both TT and anti-CD3 were reduced compared with responses by PB. In contrast, the SF response to purified protein derivative was maintained, and that to AP-MT was significantly increased, compared with PB. SF responses to AP-MT antigens were significantly greater than those to TT. The AP-MT activation of T lymphocytes from RA SF was characterized by an earlier peak proliferative response than that noted with matched PB. AP-MT responsiveness was not restricted to HLA-DR4 positive patients. These observations suggest that an epitope(s) contained within the MT complex of antigens, and enriched in the AP-MT complex, may be important in maintaining the chronic inflammation in at least some patients with RA.

Limited proliferative response to type II collagen in rheumatoid arthritis.

In order to define the potential importance of type II collagen in the activation of rheumatoid arthritis (RA) synovial fluid (SF) lymphocytes, we examined the proliferative response of matched peripheral blood and SF lymphocytes to type II collagen. The mean proliferative response to the collagen was somewhat greater (p less than 0.05) with SF, compared to peripheral blood lymphocytes. However, the magnitude of this response was relatively weak as determined by stimulation indices, and it did not approach that observed with peripheral blood lymphocytes in response to tetanus toxoid. Sixty-seven percent of peripheral bloods and 50% of SF demonstrated positive responses to the control antigen, tetanus toxoid. In contrast, only 6 and 28%, respectively, were positive in response to type II collagen. The addition of exogenous interleukin 2 augmented responses to the tetanus toxoid, however, no such enhancement with type II collagen was noted in our patients. Our collagen was arthritogenic in experimental animals. These observations do not support the existence of T cell specificity toward type II collagen as a common mechanism for the expansion of synovial lymphocytes in RA.