A role for IFN-gamma in primary and secondary immunity generated by NK cell-sensitive tumor-expressing CD80 in vivo.
We have investigated the primary and secondary immunity generated in vivo by a MHC class I-deficient tumor cell line that expressed CD80 (B7-1). CD80 expression enhanced primary NK cell-mediated tumor rejection in vivo and T cell immunity against secondary tumor challenge. CD80 expression enhanced primary NK cell-mediated tumor rejection, and both NK cell perforin and IFN-gamma activity were critical for the rejection of MHC class I-deficient RMA-S-CD80 tumor cells. This primary rejection process stimulated the subsequent development of specific CTL and Th1 responses against Ags expressed by the MHC class I-deficient RMA-S tumor cells. The development of effective secondary T cell immunity could be elicited by irradiated RMA-S-CD80 tumor cells and was dependent upon NK cells and IFN-gamma in the priming response. Our findings demonstrate a key role for IFN-gamma in innate and adaptive immunity triggered by CD80 expression on tumor cells.
Kelly
Janice M
JM
Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia.
Takeda
Kazuyoshi
K
Darcy
Phillip K
PK
Yagita
Hideo
H
Smyth
Mark J
MJ
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma