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- Title
Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance.
- Authors
Wells, A D; Li, X C; Li, Y; Walsh, M C; Zheng, X X; Wu, Z; Nuñez, G; Tang, A; Sayegh, M; Hancock, W W; Strom, T B; Turka, L A
- Abstract
The mechanisms of allograft tolerance have been classified as deletion, anergy, ignorance and suppression/regulation. Deletion has been implicated in central tolerance, whereas peripheral tolerance has generally been ascribed to clonal anergy and/or active immunoregulatory states. Here, we used two distinct systems to assess the requirement for T-cell deletion in peripheral tolerance induction. In mice transgenic for Bcl-xL, T cells were resistant to passive cell death through cytokine withdrawal, whereas T cells from interleukin-2-deficient mice did not undergo activation-induced cell death. Using either agents that block co-stimulatory pathways or the immunosuppressive drug rapamycin, which we have shown here blocks the proliferative component of interleukin-2 signaling but does not inhibit priming for activation-induced cell death, we found that mice with defective passive or active T-cell apoptotic pathways were resistant to induction of transplantation tolerance. Thus, deletion of activated T cells through activation-induced cell death or growth factor withdrawal seems necessary to achieve peripheral tolerance across major histocompatibility complex barriers.
- Publication
Nature medicine, 1999, Vol 5, Issue 11, p1303
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/15260