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Peripheral Deletion of Antigen-Specific T Cells Leads to Long-Term Tolerance Mediated by CD8⁺ Cytotoxic Cells¹

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110

Peripheral deletion is one mechanism by which potentially self-reactive clones are removed whether they escape thymic deletion. We have examined the consequences of deleting Ag-specific T cells by i.v. injection of soluble Ag. Deletion of DO11.10 T cells by peptide was mediated predominately via a Fas/FasL mechanism. Animals that underwent deletion were tolerant to subsequent immunization with Ag, even when tolerant mice were given fresh Ag-specific DO11.10 T cells before immunization. Tolerance was mediated by CD8⁺ T cells that killed the DO11.10-transgenic T cells in vivo. These data demonstrate that the programmed cell death of large numbers of T cells leads to peripheral tolerance mediated by CD8⁺ CTLs.

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