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J. Exp. Med.,
Volume 187, Number 9, May 4, 1998 1427-1438
By
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 V
8+ 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 V8+ 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.
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