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The Journal of Immunology, 2002, 168: 4960-4967.
Copyright © 2002 by The American Association of Immunologists

Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease1

Linda A. Trimble*, Kenya A. Prince*, Gary A. Pestano*, John Daley{dagger} and Harvey Cantor2,*,{ddagger}

Departments of * Cancer Immunology and AIDS and {dagger} Adult Oncology, Dana-Farber Cancer Institute, and {ddagger} Department of Pathology, Harvard Medical School, Boston, MA 02115

MHC/self peptide interactions with cognate coreceptor/TCR complexes are central to homeostasis of the T cell repertoire. Recent reports have also underlined the critical role of IL-15/IL-2 cytokines in regulating this homeostatic process. In this study, we investigate mechanisms that regulate potentially autoreactive CD8 cells that have escaped intrathymic selection. These cells, upon exit from the thymus, express high levels of CD44, B220, and the IL-15R/IL-2R, and undergo fas-dependent apoptosis. Defects in fas signaling allow increased IL-15/IL-2-dependent survival of these CD44/B220+ CD8+ as well as the double-negative T cells characteristic of lpr disease.




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