Selecting the Thymic Rank and File

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Science  25 May 2007:
Vol. 316, Issue 5828, pp. 1101
DOI: 10.1126/science.316.5828.1101c

During their passage through the thymus, developing T cells are selected on the basis of their capacity to recognize foreign antigens while remaining tolerant of the body's own constituents. This is achieved in part through interacting (in the thymic medulla) with specialized epithelial cells that offer up small samples of self proteins whose expression is largely restricted to other tissues. This supplemental expression of the self proteins is regulated by the transcription factor Aire and contributes to preventing autoimmunity.

Rossi et al. used organ cultures derived from fetal mouse thymus to ascertain that hematopoietic cells already known to induce peripheral lymphoid tissue, and aptly named lymphoid tissue inducing (LTi) cells, also regulate the development of a subset of medullary epithelial cells and their expression of Aire. This depended on the receptor activator nuclear factor-κB ligand (RANKL), and autoimmunity-like symptoms ensued after the transplantation of RANK-deficient thymus into athymic mice. Previous studies have reported that another tumor necrosis factor family member (lymphotoxin-α) is expressed in LTi cells and has similar effects, so resolving the contributions of each in regulating immunological tolerance will be of interest. — SJS

J. Exp. Med. 204, 10.1084/jem.20062497 (2007).

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