J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/263/10 $2.00
Volume 185 January 1997 263-272

Negative Selection in the Thymus Includes Semimature T Cells

By Hidehiro Kishimoto and Jonathan Sprent

From the Department of Immunology, IMM4, The Scripps Research Institute, La Jolla, California 92037

The thymic medulla plays a key role in negative selection (self-tolerance induction) and contains differentiated T cells en route to the extrathymic environment. However, being relatively mature, medullary T cells are thought to be beyond the stage of tolerance induction. This paradox is resolved by the finding that medullary T cells (CD4⁺8 thymocytes) comprise two distinct subsets. Medullary thymocytes expressing a fully mature (HSA^lo) phenotype are strongly resistant to tolerance induction, whereas cells with a semimature (HSA^hi) phenotype are tolerance susceptible. These findings suggest that the differentiated T cells reaching the medulla from the cortex remain sensitive to tolerance induction for a brief period before acquiring a fully mature tolerance-resistant phenotype. The semimature subset of medullary T cells displays unique requirements for tolerance induction; depending upon the conditions used, tolerizing these cells can involve either a Fas (CD95)-dependent or a Fas-independent pathway.

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