Abatacept modulates human dendritic cell-stimulated T-cell proliferation and effector function independent of IDO induction

Abatacept, the first in a new class of agents for RA, modulates CD28-mediated T-cell costimulation. Abatacept was evaluated for its ability to regulate human T-cell proliferation and cytokine production initiated by dendritic cells. Abatacept reduced T-cell proliferation by >95% at concentrations between 0.3 and 3 mu g/ml. The effect of abatacept on T-cell proliferation was not through induction of IDO activity, as no increase in IDO mRNA or kynurenine was observed and 1-methyl-D-tryptophan did not reverse the inhibition. In addition to the effect of abatacept on proliferation, T-cell. cytokines, IL-2, TNF alpha and IFN gamma were also reduced. Abatacept also inhibited proliferation and cytokine production in a T-cell memory response. These data demonstrate that abatacept, independent of IDO activity, attenuates both naive and memory T-cell proliferation and effector function. Taken together, these data aid our understanding of the mechanism for efficacy of abatacept in patients with autoimmune disease. (C) 2007 Elsevier Inc. All rights reserved.