Antigen - specifi c peripheral shaping of the natural regulatory T cell population Stephanie

The Rockefeller University Press $30.00 J. Exp. Med. Vol. 205 No. 13 3105-3117 www.jem.org/cgi/doi/10.1084/jem.20081359 3105 The importance of natural Foxp3 + T reg cells for the maintenance of self-tolerance was recently reaffi rmed by the observation that acute depletion of T reg cells creates a state of “ immunologic anarchy ” resulting in the rapid death of a previously healthy animal ( 1, 2 ). T reg cells are commonly thought to be generated in the thymus because of recognition of self-antigens ( 3, 4 ), which is supported by studies using mice with limited TCR diversity showing strong similarity between the thymic and peripheral T reg TCR repertoires ( 5 – 7 ). However, the peripheral and thymic T reg TCR repertoires were not identical, suggesting that certain TCRs are preferentially enriched or deleted in the periphery, akin to earlier observations in the total CD4 +