Tumor Recognition and Self-Recognition Induce Distinct Transcriptional Profiles in Antigen-Specific CD4 T Cells
| Autor: | Timothy J. Harris, Adam J. Adler, Hung-Rong Yen, Tullia C. Bruno, Satoshi Wada, Robert W. Georgantas, Chunfa Jie, Charles G. Drake, Monica V. Goldberg, Derese Getnet, Drew M. Pardoll, Joseph F. Grosso, Edward L. Hipkiss, Charles H. Maris |
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| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Transcription Genetic T cell Immunology Population Down-Regulation Hemagglutinin (influenza) Biology Article Mice Prostate cancer Immune system Neoplasms medicine Animals Immunology and Allergy Antigens education Cell Proliferation education.field_of_study Gene Expression Profiling Forkhead Transcription Factors medicine.disease Phenotype Molecular biology Rats Up-Regulation medicine.anatomical_structure Cancer research biology.protein Tramp |
| Zdroj: | The Journal of Immunology. 182:4675-4685 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0803400 |
| Popis: | Tumors express a wide variety of both mutated and nonmutated Ags. Whether these tumor Ags are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (HA) is specifically expressed in the tumor (ProHA × TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-Ag (C3HAhigh), we examined the transcriptional profile of CD4 T cells undergoing Ag-specific division. Consistent with our previous data, transfer of Ag-specific CD4 T cells into C3HAhigh resulted in a functionally inactivated CD4 T cell profile. Conversely, adoptive transfer of an identical CD4 T cell population into ProHA × TRAMP mice resulted in the induction of a regulatory phenotype of the T cell (Treg) both at the transcriptional and functional level. Interestingly, this Treg skewing was a property of even early-stage tumors, suggesting Treg induction as an important tolerance mechanism during tumor development. |
| Databáze: | OpenAIRE |
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