Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
Date (from‐to) : 2012/04 -2015/03
Author : MAEDA Shinji
Regulatory T cells (Tregs) play an important role in self-tolerance, whereas various inflammatory conditions, such as rheumatoid arthritis (RA), attenuate the suppressive function. The purpose of this study is to clarify the modulation of Tregs by agents affecting T cell signaling, providing a basis for novel therapeutic approach for immunological remission.
We have examined the change of phenotypes and the amount of circulating Tregs in human (RA) and mice (BALB/c, Collagen antibody induced arthritis,CAIA) in vivo. In mice, Tregs are increased by mTOR inhibitor (Everolimus) and IL-2CAc (IL-2 cytokine/mIL-2 antibody (JES6-1) complexes). Furthermore, maximum arthritis severity are significantly attenuated by IL-2CAc. In humans with RA, after 4wks CTLA-4-Ig (Abatacept) therapy, the ratio of resting Tregs in CD4 + T cells significantly increased, whereas activated Tregs decreased. Altering T cell signaling using various agents can control Tregs.