Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self

Speaker: 呂秀菱                              Time: 15:10 ~ 16:00

Commentator: 黎煥耀 老師            Place: 601

Abstract:

In the healthy individual, the immune system must be delicately balanced between self-antigen tolerance and pathogen-drived immunity. Although in central tolerance, medullary thymic epithelial cells (mTECs) express many peripheral-tissue antigens (PTAs) through both MHC class I and class II molecules to delete self-reactive T cells ¹, but it is not sufficient.² Peripheral tolerance is therefore required to eliminate or inactivate self-reactive T cells to protect vital tissues from autoimmune attack. Dendritic cells acquire parenchymal tissue antigens, transport them to nearby lymph node, and present them to circulating T cells under non-inflammatory condition. Take intestinal tissue for example, however, peripheral tolerance occurs in traditional pathway is seemingly impossible because intestine interacts with profuse microbes and inflammation always happens. The authors proposed there must be an induction of tolerance before T cells contact with intestinal tissue. They found that lymph node stromal cells have similar functions as mTECs. These cells present endogenously expressed PTAs, express PTAs-regulating genes, and present peptides through both MHC class I and class II molecules to induce T cell tolerance, especially CD8⁺ T cells.³ Besides intestinal tissue, many other peripheral antigens are endogenously expressed in these stromal cells. Together, peripheral tolerance takes place not only by antigen presenting cells in lymph node close to the captured tissue, but also stromal cells in all body lymph nodes to efficiently induce T cell tolerance to the tissue-specific antigens.

References:

1.     Kyewski, B. & Klein, L. A central role for central tolerance. Annu. Rev. Immunol. 24: 571-606, 2006.

2.     Gallegos, A.M. & Bevan, M.J. Central tolerance: good but imperfect. Immunol. Rev. 209: 290-296, 2006.

3.     Lee, J.W. et al. Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat. Immunol. 8: 181-190, 2007.