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Publication : A role for Fas in negative selection of thymocytes in vivo.

First Author  Kishimoto H Year  1998
Journal  J Exp Med Volume  187
Issue  9 Pages  1427-38
PubMed ID  9565635 Mgi Jnum  J:112083
Mgi Id  MGI:3655458 Doi  10.1084/jem.187.9.1427
Citation  Kishimoto H, et al. (1998) A role for Fas in negative selection of thymocytes in vivo. J Exp Med 187(9):1427-38
abstractText  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 microg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vbeta8+ 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 Vbeta8+ 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 microg) but not by high doses (100 microg). 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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