Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells

Derese Getnet, Charles H. Maris, Edward L. Hipkiss, Joseph F. Grosso, Timothy J. Harris, Hung Rong Yen, Tullia C. Bruno, Satoshi Wada, Adam Adler, Robert W. Georgantas, Chunfa Jie, Monica V. Goldberg, Drew M. Pardoll, Charles G. Drake

Research output: Contribution to journalArticle

Abstract

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 x 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 x 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.

Original languageEnglish (US)
Pages (from-to)4675-4685
Number of pages11
JournalJournal of Immunology
Volume182
Issue number8
DOIs
StatePublished - Apr 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Getnet, D., Maris, C. H., Hipkiss, E. L., Grosso, J. F., Harris, T. J., Yen, H. R., Bruno, T. C., Wada, S., Adler, A., Georgantas, R. W., Jie, C., Goldberg, M. V., Pardoll, D. M., & Drake, C. G. (2009). Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells. Journal of Immunology, 182(8), 4675-4685. https://doi.org/10.4049/jimmunol.0803400