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© The Rockefeller University Press, 0022-1007/1997/1/263/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 2, January 20, 1997 263-272

Articles

Negative Selection in the Thymus Includes Semimature T Cells

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 (HSAlo) phenotype are strongly resistant to tolerance induction, whereas cells with a semimature (HSAhi) 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.

Address correspondence to Jonathan Sprent, Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037.

We wish to express our thanks to Dr. David Lynch and Immunex for providing Fas–Ig and to Ms. Barbara Marchand for typing the manuscript.

This work was supported by grants CA38355, CA25803, AI21487, and AI32068 from the United States Public Health Service. Dr. Hidehiro Kishimoto is the recipient of a fellowship from the Cancer Research Institute. This is publication number 9928-IMM from The Scripps Research Institute.

1Abbreviations used in this paper: AICD, activation-induced cell death; BM, bone marrow; C, constant; DP, double positive; FasL, Fas ligand; HSA, heatstable antigen; PI, propidium iodide; SP, single positive; TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling.


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