| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Outline of Final Research Achievements |
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.
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