Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers for B cell differentiation

Abstract

Objective: To delineate the phenotype and function of synovial T cells in rheumatoid arthritis (RA).

Methods: T cells from normal subjects or from RA peripheral blood (PB), synovial fluid (SF), or synovial tissue (ST) were analyzed phenotypically and functionally.

Results: RA SF and ST T cells were found to be markedly enriched in CD45RAdim, CD45RO+, CD45RBdim mature memory cells, whereas in the PB, CD45RAbright naive T cells were more frequent than CD45RO+ memory T cells, and only a minority were CD45RBdim. SF and ST T cells proliferated less well and produced less interleukin-2 in response to mitogenic stimuli than did PB T cells. However, synovial T cells effectively promoted the production of Ig from normal B cells. Moreover, PB and synovial T cells differed in their capacity to down-regulate immunoglobulin production. Anti-CD3-stimulated PB T cells suppressed Ig production unless their proliferation was prevented with mitomycin C. In contrast, synovial T cells were potent helpers of B cell Ig production regardless of antecedent treatment with mitomycin C. To examine the relationship between the CD45RBdim phenotype and B cell help, CD45RBdim T cells were sorted from PB. As opposed to the findings with synovial T cells, suppression by control PB CD45RBdim T cells was observed, but only when large numbers were employed. B cell Ig production was enhanced after treatment of PB CD45RBdim T cells with mitomycin C. In contrast, healthy control sorted CD45RBbright or sorted CD4+, CD45RO+, CD45RBbright T cells did not support Ig secretion. After treatment with mitomycin C, both of these populations were more effective helpers of Ig production.

Conclusion: RA synovium is enriched in differentiated CD45RBdim memory T cells with potent helper activity and diminished capacity to down-regulate B cells, strongly implying an active role for these cells in the production of Ig in the synovium, and thus in the propagation of disease.