Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells (Nat Immunol, 2007, 8:351-358)

報告日期: 2007/10/23
報告時間: 16:00/16:50
報告學生: 黃思偉(英文報告)
講評老師: 楊倍昌
附件下載:

Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells

Nature Immunology, 8: 351-358 (2007)

 

Speaker: Szu-Wei Huang

 

Commentator: Dr. Bei-Chang Yang

 

Place: Room 602

Date:10/23/2007 16:00~17:00

Abstract:

It still remains unclear how and where autoreactive CD4+ thymocytes undergo negative selection or positive selection into regulatory T cells. In order to answer these questions, the authors transplanted reaggregate thymic organ cultures (RTOC) in a mixture of wild-type and MHC-II deficient thymi into MHC-II deficient recipient mice resulting in grafts compartmentalized into cortical and medullary regions composed of either MHC-II positive or negative cells, and only in MHC-II positive medullary regions could they find significantly more Foxp3+ Treg cells. Early studies have indicated that autoimmune regulator (Aire) regulates promiscuous expression of tissue-specific antigens in medullary thymic epithelial cells (mTEC) contributing to negative selection in central tolerance, but it arouses a question if Aire is also important in positive selection for regulatory T cells. Thus, the authors further demonstrated that only mTECs, especially the MHC-II-high B7.1hi ones, predominantly express Aire, and there is generation of functional hemaggulutinin (HA)-specific regulatory T cells in chimera mice within an Aire-driven HA expression and HA-autoreactive background. Furthermore, in a series of chimera experiments, the authors showed that if there is no Aire+ mTEC expressing specific antigen, even though there is dendritic cell, no generation of antigen-specific regulatory T cell is noted. In conclusion, their findings prove that Aire+ mTECs expressing tissue-specific antigen are exclusively required for generation of autoreactive regulatory T cells.

 

 

 

 

 

 

 

 

 

 

Reference:

 

 

 

 

1.

Aschenbrenner, K. et al. Selection of Foxp3+ regulatory T cells specific for self antigen

expressed and presented by Aire+ medullary thymic epithelial cells. Nature immunology

8, 351-358 (2007).

2.

Soumelis, V. & Liu, Y.J. Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation. Springer seminars in immunopathology 25, 325-333 (2004).