T cell reactivity to Epstein-Barr virus in rheumatoid arthritis

Abstract

The notion that T cells could play a central role in rheumatoid arthritis (RA) emerged in the late 70’s with the demonstration of massive T cell infiltration in inflamed joints from RA patients [1]. Support for this hypothesis later came from studies showing (i) an increased susceptibility to RA associated with expression of particular HLA-DR alleles [2], (ii) an increased expression of activation and memory markers by joint-infiltrating lymphocytes [3-6], (iii) T cell repertoire biases within joint-infiltrating lymphocytes when compared to peripheral blood T cells (reviewed in [7,8]), and (iv) beneficial effects of T cell-depleting or suppressive treatments in RA patients [9-11]. However, in the absence of any direct evidence for a pathogenic role of T cells in RA and in light of the limited therapeutic effects of antibody-mediated T cell depletion in some clinical trials, the paradigm of RA as a T cell-mediated disease has more recently been put into question [12,13]. Here we would like to present and discuss recent observations from our laboratory that may revive this paradigm and support an implication of common intracellular parasites, such as Epstein-Barr virus (EBV), in the perpetuation of T cell-dependent joint erosion during chronic RA. At the present stage our observations, which demonstrate the frequent occurrence of EBV-reactive T cells in inflamed joints from chronic RA patients [14,15), raise many more questions than they provide answers. However, several testable hypotheses may account for these findings and these will be presented here.