Cited by 77T-cell and B-cell ImmunologyReproductive System and PregnancyImmunotherapy and Immune Responses

Activation-induced apoptosis of autoreactive and alloreactive T lymphocytes in the target organ as a major mechanism of tolerance

Pender, Michael P·1999·Immunology & Cell Biology

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.

Integrity signals

Registry

Crossref · 10.1046/j.1440-1711.1999.00818.x

Cites

85 of 85 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Increased levels of gene expression resulting from higher vector doses promote immune tolerance through elevated expression of IL-10, enhanced apoptosis of effector T cells, and enhanced Treg induction.

    “However, the exact opposite is true, and increased levels of gene expression resulting from higher vector doses promote immune tolerance through elevated expression of the immune suppressive cytokine IL-10, enhanced apoptosis of effector T cells, and enhanced Treg induction similar to that observed with a very high HBV inoculum in chimpanzees.15,56,57,58,59,60,61,62”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Pender, M. P.
Affiliations
The University of Queensland (AU)
Corresponding author
Pender, Michael P
Venue
Immunology & Cell Biology
Publisher
Wiley
Published
1999-06
Volume
77
Issue
3
Pages
216-223
ISSN
  • 0004-945X (ISSN-L)
  • 0818-9641
  • 1440-1711
OpenAlex
W2077153831
Cited by
77
References
85
Citations by year
2023: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 2
FWCI
0.84
Type
journal article
Language
en
Open access
closed
Locations
  • Immunology and Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Health and Medical Research Council of Australia
  • National Multiple Sclerosis Society of Australia
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
activation-induced cell death, immune tolerance, autoreactive T cells, alloreactive T cells, costimulation, target organs, autoimmune disease, allograft acceptance, MHC mismatch, liver transplantation, memory T cells
MeSH terms
Animals, Antigen-Presenting Cells, Autoimmune Diseases, Encephalomyelitis, Autoimmune, Experimental, Humans, Immune Tolerance, Lymphocyte Activation, Multiple Sclerosis, T-Lymphocytes, Autoimmunity, Apoptosis, fas Receptor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review