The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/5/1427/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 9, May 4, 1998 1427-1438

Articles

A Role for Fas in Negative Selection of Thymocytes In Vivo

Hidehiro Kishimoto, Charles D. Surh, and Jonathan Sprent

From the Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1–100 µg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vβ8+ cells at the level of the semi-mature population of HSAhi CD4+ 8– cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vβ8+ HSAhi CD4+ 8– thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (≤1 µg) but not by high doses (100 µg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.

Address correspondence to Jonathan Sprent, Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, California 92037. Phone: 619-784-8619; Fax: 619-784-8839; E-mail: jsprent{at}scripps.edu

This is publication no. 10869-IMM from the Scripps Research Institute.

Abbreviations used: AICD, activation-induced cell death; BrdU, bromodeoxyuridine; DP, double positive; guinea pig C, guinea pig complement; HSA, heat-stable antigen; ova, ovalbumin; SEB, staphylococcal enterotoxin B; SP, single positive; TUNEL, TdT-mediated dUTP-biotin nick end labeling.


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