A critical role of T cell antigen receptor-transduced MHC class I-restricted helper T cells in tumor protection

Emma C Morris, Aristotle Tsallios, Gavin M Bendle, Shao-An Xue, Hans J Stauss

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

Adoptive transfer of antigen-specific CD4(+) and CD8(+) T cells is one of the most efficient forms of cancer immunotherapy. However, the isolation of antigen-specific CD4(+) T cells is limited because only few tumor-associated helper epitopes are identified. Here, we used T cell antigen receptor gene transfer to target CD4(+) T cells against an MHC class I-presented epitope of a model tumor antigen. IFN-gamma-producing CD4(+) T cells were unable to expand in vivo and to provide help for tumor rejection. In contrast, CD4(+) T cells producing high levels of IL-2 expanded in vivo, provided help for cytotoxic T lymphocyte-mediated tumor rejection, and developed T cell memory. The data demonstrate in vivo synergy between T cell antigen receptor-transduced CD4(+) and CD8(+) T cells specific for the same epitope resulting in long-term tumor protection.
Original languageEnglish
Pages (from-to)7934-9
Number of pages6
JournalNational Academy of Sciences. Proceedings
Volume102
Issue number22
DOIs
Publication statusPublished - 31 May 2005

Keywords

  • Animals
  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes
  • Epitopes
  • Histocompatibility Antigens Class I
  • Immunologic Memory
  • Immunotherapy, Adoptive
  • Interleukin-2
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms
  • Receptors, Antigen, T-Cell
  • Retroviridae
  • Spleen
  • T-Lymphocytes, Helper-Inducer
  • Transduction, Genetic

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