COEXPRESSION OF THE CD45RA AND CD45RO ANTIGENS ON T-LYMPHOCYTES IN CHRONIC ARTHRITIS

The site of T lymphocyte activation in chronic arthritis is unknown. P eripheral blood (PB) lymphocytes from chronic arthritis patients are i n a 'naive' or non-activated state, as defined by expression of the CD 45RA antigen and lack of HLA class II expression. In contrast, most sy novial fluid (SF)T lymphocytes express a 'memory' or activated phenoty pe, as defined by the CD45RO antigen and high HLA class II expression. Following stimulation, naive cells lose CD45RA and gain CD45RO expres sion to become memory cells with a transitional stage of dual CD45RA, CD45RO antigen expression. To localize where this change in phenotype occurs we used dual colour immunofluorescence labelling to compare the percentage of dual CD45RA, CD45RO-positive T Iymphocytes in PB and SF from chronic arthritic patients and from normal PB, assuming this pop ulation would be increased at the primary site of T lymphocyte activat ion. Expression of the intermediate and late activation marker, HLB-DR , was also analysed using dual colour immunofluorescence labelling. Th e percentage of dual positive T lymphocytes was similar between arthri tic PB, SF, and normal PB, as was the density of both CD45RA and CD45R O antigens. Thus, CD45 isoform expression did not indicate where T Iym phocytes were activated. However, we identified a previously unreporte d population of CD45RA(+) CD45RO(+) HLA-DR(-) lymphocytes in arthritic and normal PB. In SF, this population was absent, but a substantial n umber of dual CD45RA, CD45RO-positive HLA-DR(+) T lymphocytes were ide ntified. This population would not be predicted by the current model o f T lymphocyte activation. Division of T lymphocytes into functional g roups on the basis of CD45 isoform expression is likely to be more com plicated than previously thought. Based on our findings we propose an alternative model of T lymphocyte differentiation.