Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation (Nat Med, 2007, 13:423-431)

報告日期: 2007/10/23
報告時間: 15:10/16:00
報告學生: 沈芳秀
講評老師: 黎煥耀
附件下載:

Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation

 

Nature Medicine 13: 423-431 (2007)

 

 

Speaker: Fang-Hsiu Shen 

Commentator: Dr. Huan-Yao Lei

Time: , Oct. 23

Room: 602

 

Regulatory T cells (T-reg) play important roles in maintaining peripheral tolerance and controlling autoimmunity by suppressing pathogenic autoreactive T cell. Furthermore, antigen-specific T-reg have been demonstrated to reduce the damage in autoimmune disease models like type I diabetes, multiple sclerosis, and rheumatoid arthritis. However, it is uncertain whether these antigen-specific T-reg will proliferate under specific-antigen stimulations and be recruited to the inflammatory site during the autoimmune response. In this study, the author developed Foxp3gfp knock-in mice and used myelin oligodendrocyte glycoprotein (MOG)35-55/IAb tetramers to track autoantigen-specific T-reg and effector T cells (T-eff) in vivo during experimental autoimmune encephalomyelitis (EAE). They found marked expansion after MOG-specific-antigen stimulation in peripheral lymphoid tissues and increased T-reg infiltration in the central nervous system (CNS) during EAE. Although antigen-specific T-reg were efficient in suppressing MOG-specific responses of naïve T cells, they failed to suppress the MOG-specific T-eff isolated from the CNS during acute phase of EAE. Resistance of MOG-specific T-eff to T-reg suppression was due to the inflammatory environment. During the peak of EAE, MOG-specific T-eff in the CNS secreted more IL-6 and TNF-α, which were responsible for the inability of MOG-specific T-reg to inhibit T-eff. Therefore, local inflammatory environment should be taken into consideration when using T-reg as a therapeutic agent to control autoimmune diseases.

 

 

References

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2. Naturally arising Foxp3-expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 6: 345-352(2005)