Autoaggression and tumor rejection: it takes more than self-specific T-cell activation
Summary: Establishment of self-tolerance prevents autoaggression against organ-specific self-antigens. This beneficial effect, however, may In turn be responsible for tumor immune evasion. Thus, dissecting the mechanisms leading to the breakdown of self-tolerance in autoimmune diseases might provide...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
28 April 2006
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| In: |
Immunological reviews
Year: 1999, Volume: 169, Issue: 1, Pages: 263-272 |
| ISSN: | 1600-065X |
| DOI: | 10.1111/j.1600-065X.1999.tb01321.x |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1600-065X.1999.tb01321.x Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-065X.1999.tb01321.x 
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| Author Notes: | Ruth Ganss, Andreas Limmer, Torsten Sacher, Bernd Arnold, Günter J. Hämmerling |
| Summary: | Summary: Establishment of self-tolerance prevents autoaggression against organ-specific self-antigens. This beneficial effect, however, may In turn be responsible for tumor immune evasion. Thus, dissecting the mechanisms leading to the breakdown of self-tolerance in autoimmune diseases might provide insights for successful antitumor immune therapies. In a variety of animal models, organ- or tumor-specific immunity has been described, focusing on antigen-specific T-cell activation. Here, we discuss two trans -genic mouse models which demonstrate that both autoaggression and tumor rejection require more than activated, self-reactive T cells. TCR transgenic mice, which are tolerant to a liver-specific MHC class I antigen, Kb, can be activated to reject Kbb-positive grafts, but fail to attack Kb-expressing liver. However, autoaggression occurs when activated T cells are combined with “conditioning” of the target organ by irradiation or infection with a liver-specific pathogen. Similarly, in a mouse model of islet cell carcinoma, neither co-stimulatory tumor cells nor highly activated antitumor lymphocytes provoke an effective immune response against the tumor. Instead, a combination of activated lymphocytes and irradiation is required for lymphocyte infiltration into solid tumors. Both model systems provide evidence that although activated antigen-specific lymphocytes are a prerequisite for autoaggression, effector cell extravasation and appropriate interaction with the target organ/tumor are equally important. Thus, we propose that the organ/tumor microenvironment is a critical parameter in determining the effectiveness of an anti-self immune response. |
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| Item Description: | First published: 28 April 2006 Elektronische Reproduktion der Druck-Ausgabe Gesehen am 16.02.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1600-065X |
| DOI: | 10.1111/j.1600-065X.1999.tb01321.x |