Th1 and Th2 cell clones to a poorly immunogenic tumor antigen initiate CD8+ T cell-dependent tumor eradication in vivo.
Although CD8(+) T cells play a central role as immune effectors, CD4(+) T cells act to control the activation and persistence of the CD8(+) T cell response in autoimmune disease, antiviral immunity, and experimental systems with immunogenic model tumor Ag. However, little information is available on the effects of CD4(+) T cells on the function of endogenous CD8(+) T lymphocytes recognizing authentic tumor rejection Ag with limited immunogenicity. We report here that the prophylactic or postchallenge administration of T helper Th1-type and Th2-type CD4(+) clones specific for an unmutated rejection Ag (murine P815AB, resembling tumor-specific shared Ag in humans) leads to the induction of P815AB-specific reactivity in vivo and concomitant tumor destruction, with quantitative rather than qualitative differences characterizing the antitumor activity of Th1 vs Th2 cells. Because the transferred CD4(+) cells lacked direct antitumor activity in vitro and required the de novo generation of P815AB-specific CD8(+) T cells in vivo, these findings suggest that CD4(+) lymphocytes can enhance the ability of host APC to initiate an endogenous CD8(+) T cell response to authentic, poorly immunogenic tumor rejection Ag.
Fallarino
F
F
Department of Experimental Medicine, University of Perugia, Perugia, Italy.
Grohmann
U
U
Bianchi
R
R
Vacca
Carmine
C
Fioretti
M C
MC
Puccetti
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology / Q000637:transplantation; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology / Q000637:transplantation*; D018418:Th2 Cells / Q000276:immunology / Q000637:transplantation*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D009842:Oligopeptides