Several Different Cell Surface Molecules Control Negative Selection of Medullary Thymocytes

doi:10.1084/jem.190.1.65

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J. Exp. Med., Volume 190, Number 1, July 5, 1999 65-74
Copyright © 1999 by The Rockefeller University Press.

Several Different Cell Surface Molecules Control Negative Selection of Medullary Thymocytes

Hidehiro Kishimoto^a and Jonathan Sprent^a
^a From the Department of Immunology, The Scripps Research Institute, La Jolla, California 92037

Correspondence to: Jonathan Sprent

Repeated attempts to show that costimulation for negative selectionis controlled by a single cell surface molecule have been unsuccessful.Thus, negative selection may involve multiple cell surface moleculesacting in consort. In support of this idea, we show here thatat least three cell surface molecules, namely CD28, CD5, andCD43, contribute to Fas-independent negative selection of thetolerance-susceptible population of heat-stable antigen (HSA)^hiCD4⁺8^-cells found in the medulla. The costimulatory function of thesethree molecules can be blocked by certain cytokines, IL-4 andIL-7, and coinjecting these cytokines with antigen in vivo abolishesnegative selection; Fas-dependent negative selection, however,is maintained. The results suggest that efficient negative selectionrequires the combined functions of at least four cell surfacemolecules: CD28, CD5, CD43, and Fas.

Key Words: thymus, tolerance, costimulatory signals, lymphokines, medulla

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