Activation-Induced Apoptosis of Autoreactive and Alloreactive T Lymphocytes in the Target Organ as a Major Mechanism of Tolerance

Pender, Michael P. (1999) Activation-Induced Apoptosis of Autoreactive and Alloreactive T Lymphocytes in the Target Organ as a Major Mechanism of Tolerance. Immunology and Cell Biology, 77 3: 216-223. doi:10.1046/j.1440-1711.1999.00818.x

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Author Pender, Michael P.
Title Activation-Induced Apoptosis of Autoreactive and Alloreactive T Lymphocytes in the Target Organ as a Major Mechanism of Tolerance
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
Publication date 1999-07-01
Sub-type Article (original research)
DOI 10.1046/j.1440-1711.1999.00818.x
Open Access Status File (Author Post-print)
Volume 77
Issue 3
Start page 216
End page 223
Total pages 8
Place of publication Carlton, Vic, Aust.
Publisher Blackwell Science Asia
Collection year 1999
Language eng
Subject 320200 Immunology
320207 Autoimmunity
Abstract Normal individuals have mature T lymphocytes that are capable of reacting to self-antigens and can be activated by cross-reacting environmental antigens. The mechanism that maintains immune tolerance and prevents these activated autoreactive T cells from causing autoimmune disease is unclear. We have previously hypothesized that activation-induced apoptosis of previously activated autoreactive T cells in the target organ is a major mechanism for maintaining tolerance. Here I review the current evidence to support this hypothesis. It is proposed that when activated autoreactive T cells enter the target organ, they are reactivated mainly by non-professional antigen-presenting cells (APC) and deleted by activation-induced apoptosis through the Fas (CD95) pathway before producing significant target organ damage. This apoptosis occurs because the reactivated T cells do not receive sufficient costimulation from the non-professional APC to up-regulate their expression of Bcl-2-related anti-apoptotic proteins, which inhibit the CD95 pro-apoptotic pathway. This is in contrast to the situation in peripheral lymphoid organs, where reactivation of T cells by professional APC results in sufficient costimulation-induced up-regulation of Bcl-2-related proteins to inhibit the CD95 pathway and allow T cell proliferation and survival as memory T cells. Activation-induced apoptosis of alloreactive T cells in allografts can similarly account for spontaneous allograft acceptance, as occurs after MHC-mismatched liver transplantation.
Keyword apoptosis
experimental autoimmune encephalomyelitis
immune tolerance
CD95 (Fas)
T lymphocyte
experimental allergic encephalomyelitis
Q-Index Code C1
Additional Notes This is an author version of an article originally published as Pender, M.P., Activation-induced apoptosis of autoreactive and alloreactive T lymphocytes in the target organ as a major mechanism of tolerance. Immunology and Cell Biology, 1999. 77(3): 216-23. doi: 10.1046/j.1440-1711.1999.00818.x Copyright 1999 Nature Publishing. All rights reserved. This item is freely available on the Nature Publishing site.

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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