Lymphocytes from the site of disease are functionally different from peripheral blood lymphocytes and may demonstrate etiologically related antigen specificity

Over a 12-year period, in vitro synovial lymphocyte responses to microbiological antigen stimulation were measured by the [ 3H]thymidine uptake method in referred patients with all types of non-crystal, non-septic, inflammatory arthritis. From this large study group comparisons of synovial with peripheral blood lymphocyte (PBL) responses were available in 9 patients with enteric reactive arthritis (ERA), 12 patients with sexually acquired reactive arthritis (SARA) and 18 patients with recurrent or persistent oligoarthritis or with polyarticular ‘rheumatoid’ arthritis. Employing 2-tailed t tests, analysis of variance (ANOVA) or meta-analysis, as appropriate to the obtained data, significant differences were found between synovial and peripheral blood responses. In only 2 of 9 patients with bacteriologically defined ERA, in only 4 of 12 patients with SARA and in only 2 of 18 patients with oligoarthritis or ‘rheumatoid’ arthritis did the PBLs show statistically significant responses to the antigen that elicited a significant response from synovial lymphocytes. It is concluded that lymphocytes from the site of disease are often functionally different from PBLs and may demonstrate etiologically related antigen specificity; thus they may be a preferred source of lymphocytes for the investigation of immunologically mediated disease, the etiology of which is not understood. This viewpoint is supported by a recent paper on the specificity of hepatic lymphocytes for a protein of hepatitis C in patients with chronic hepatitis C, and also by the use of tumour-infiltrating lymphocytes for anti-melanoma therapy.