Helper function of memory CD8+ T cells: heterologous CD8+ T cells support the induction of therapeutic cancer immunity.
In contrast to the well-established efficacy of preventive vaccines, the effectiveness of therapeutic vaccines remains limited. To develop effective vaccination regimens against cancer, we have analyzed the effect of effector and memory CD8+ T cells on the ability of dendritic cells to mediate the immunologic and antitumor effects of vaccination. We show that in contrast to effector CD8+ T cells that kill antigen-carrying dendritic cells, IFNgamma-producing memory CD8+ T cells act as "helper" cells, supporting the ability of dendritic cells to produce interleukin-12 (IL-12) p70. Promoting the interaction of tumor antigen-carrying dendritic cells with memory-type "heterologous" (tumor-irrelevant) CD8+ T cells strongly enhances the IL-12p70-dependent immunogenic and therapeutic effects of vaccination in the animals bearing established tumors. Our data show that the suppressive and helper functions of CD8+ T cells are differentially expressed at different phases of CD8+ T-cell responses. Selective performance of helper functions by memory (in contrast to effector) CD8+ T cells helps to explain the phenomenon of immune memory and facilitates the design of effective therapeutic vaccines against cancer and chronic infections.
Nakamura
Yutaro
Y
Department of Surgery, University of Pittsburgh, Eye and Ear Institute, PA 15213-1863, USA.
Watchmaker
Payal
P
Urban
Julie
J
Sheridan
Brian
B
Giermasz
Adam
A
Nishimura
Fumihiko
F
Sasaki
Kotaro
K
Cumberland
Rachel
R
Muthuswamy
Ravikumar
R
Mailliard
Robbie B
RB
Larregina
Adriana T
AT
Falo
Louis D
LD
Gooding
William
W
Storkus
Walter J
WJ
Okada
Hideho
H
Hendricks
Robert L
RL
Kalinski
Pawel
P
D000230:Adenocarcinoma / Q000276:immunology* / Q000628:therapy; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D019496:Cancer Vaccines