Clonal expansions in selected TCR BV families of rheumatoid arthritis patients are reduced by treatment with the TNFalpha inhibitors etanercept and infliximab.

摘要

Clonal expansions of autoreactive CD4+ T cells are frequently present in patients with rheumatoid arthritis (RA) and are stable over long periods of time. This study was undertaken to investigate the influence of anti-TNFalpha treatment on such clonal expansions in the peripheral CD4+ T-cell compartment. TNFalpha inhibiting therapies significantly reduced the total number of expanded clonotypes. This effect was mainly observed in clonal expansions in the BV6 family, while in clonal expansions of the BV14 family no such effect was seen. No change in the percentage of CD4+ CD28 null T cells was observed. Serum concentrations of the pro-homeostatic cytokine IL-7 were found to increase in patients responding TNFalpha-inhibiting therapy. These data argue for a normalization of adaptive immune mechanisms under TNFalpha inhibiting therapies, which may be secondary to the control of inflammation but contribute to the efficacy of cytokine blockade therapy.