Rapid tolerization of virus-activated tumor-specific CD8+ T cells in prostate tumors of TRAMP mice.

Abstract

To study T cell responses to tumors in an autochthonous model, we expressed a CD8 T cell epitope SIYRYYGL (SIY) in the prostate of transgenic adenocarcinoma (TRAMP) mice (referred to as TRP-SIY), which spontaneously develop prostate cancer. Naïve SIY-specific CD8 T cells adoptively transferred into TRP-SIY mice became tolerized in the prostate draining lymph nodes. Vaccination of TRP-SIY mice intranasally with influenza virus that expresses the SIY epitope resulted in generation of SIY-specific effector T cells in the lung-draining lymph nodes. These effector T cells expressed TNFalpha and IFNgamma, eliminated SIY peptide-loaded target cells in vivo, and infiltrated prostate tumors, where they rapidly lost the ability to produce effector cytokines. A population of these T cells persisted in prostate tumors but not in lymphoid organs and could be induced to re-express effector functions following cytokine treatment in vitro. These findings suggest that T cells of a given clone can be activated and tolerized simultaneously in different microenvironments of the same host and that effector T cells are rapidly tolerized in the tumors. Our model provides a system to study T cell-tumor interactions in detail and to test the efficacy of cancer immunotherapeutic strategies.

• Authors: Ailin Bai, Eileen Higham, Herman N Eisen, K Dane Wittrup, Jianzhu Chen
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 105 Issue 35 Pg. 13003-8 (Sep 02 2008) ISSN: 1091-6490 [Electronic] United States
• PMID: 18723683 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cytokines
• Epitopes, T-Lymphocyte
• Prostate-Specific Antigen

Topics

• Adenocarcinoma (immunology)
• Animals
• CD8-Positive T-Lymphocytes (immunology, virology)
• Cross-Priming (immunology)
• Cytokines (biosynthesis)
• Disease Models, Animal
• Epitopes, T-Lymphocyte (immunology)
• Immune Tolerance (immunology)
• Lymphocyte Activation (immunology)
• Male
• Mice
• Orthomyxoviridae (immunology)
• Orthomyxoviridae Infections (immunology)
• Prostate-Specific Antigen (immunology)
• Prostatic Neoplasms (immunology, virology)
• Rats
• Vaccination