Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology*
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Cell Cycle / genetics
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Cell Cycle / immunology
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Cell Death / genetics
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Cell Death / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Movement / genetics
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Cell Movement / immunology
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Clonal Deletion* / genetics
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DNA-Binding Proteins / metabolism
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Female
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H-2 Antigens / metabolism
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Homeostasis / genetics
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Homeostasis / immunology
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Hyaluronan Receptors / biosynthesis
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Leukocyte Common Antigens / biosynthesis
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Lymphoproliferative Disorders / genetics
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Lymphoproliferative Disorders / immunology*
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Lymphoproliferative Disorders / pathology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred MRL lpr
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Mice, Transgenic
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Peptide Fragments / metabolism
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Receptors, Interleukin-2 / biosynthesis
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Receptors, Interleukin-2 / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Thymus Gland / pathology
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Up-Regulation / genetics
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Up-Regulation / immunology
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fas Receptor / genetics
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fas Receptor / physiology*
Substances
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DNA-Binding Proteins
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H-2 Antigens
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H-2K(K) antigen
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Hyaluronan Receptors
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Peptide Fragments
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Rag2 protein, mouse
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Receptors, Interleukin-2
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V(D)J recombination activating protein 2
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fas Receptor
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Leukocyte Common Antigens