A critical role of T cell antigen receptor-transduced MHC class I-restricted helper T cells in tumor protection.
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.
Morris
Emma C
EC
Department of Immunology, Imperial College, Du Cane Road, London W12 0NN, United Kingdom. emma.morris@medsch.ucl.ac.uk
Tsallios
Aristotle
A
Bendle
Gavin M
GM
Xue
Shao-An
SA
Stauss
Hans J
HJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000517:prevention & control* / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012190:Retroviridae; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D014161:Transduction, Genetic
D000951:Antigens, Neoplasm; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell