Article ID Journal Published Year Pages File Type
3258314 Clinical Immunology 2008 10 Pages PDF
Abstract

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 μg/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, TNFα and IFNγ 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.

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