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Regulatory T-cell dynamics with abatacept treatment in rheumatoid arthritis.
International Reviews of Immunology 2018 May 15
The progressive damage in rheumatoid arthritis (RA) has been linked to an increase in inflammatory Th1/Th17 cells and a decrease in number or function of immunomodulatory regulatory T cells (Tregs). Many therapies that are effective in RA are shown to affect Th1/Th17 cells and/or Tregs. One such therapy, abatacept, utilizes a physiologic immunomodulatory molecule called cytotoxic lymphocyte antigen-4 (CTLA-4) which causes contact-dependent inhibition of inflammatory T-cell activation. Recent advances in CTLA-4 research has uncovered the method by which this occurs physiologically but the actions of the CTLA-4Ig fusion protein are still not fully understood. The reported effects of the drug on Treg population number and suppressor function have been very mixed. In this review, we will discuss the current literature surrounding the effects of abatacept in rheumatoid arthritis and explore potential explanations for the differences in results. Future opportunities in this area include contributions to a unified definition for different immune cell populations, LAG3+ Tregs which may pose an avenue for further study or the stratification of patients with regards to their specific disease characteristics, resulting in optimized treatment for disease remission.
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