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The Journal of Immunology, 2000, 164: 3645-3651.
Copyright © 2000 by The American Association of Immunologists

Crucial Role of TNF-{alpha} in CD8 T Cell-Mediated Elimination of 3LL-A9 Lewis Lung Carcinoma Cells In Vivo1

Armelle Prévost-Blondel*, Evelyn Roth*, Felicia M. Rosenthal{dagger} and Hanspeter Pircher2,*

* Institute of Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Freiburg, Germany; and {dagger} Cell Genix Technologie Transfer, GmbH, Freiburg, Germany

The role of perforin, IFN-{gamma}, and TNF-{alpha} in anti-tumor CD8 T cell immunity was examined in a new tumor model using a CD8 T cell epitope (GP33) derived from lymphocytic choriomeningitis virus as a tumor-associated Ag. In contrast with parental 3LL-A9 (A9) Lewis lung carcinoma cells that progressively grow in C57BL/6 mice, s.c. injection of GP33-transfected A9GP33 tumor cells induced a protective GP33-specific CD8 T cell response that led to complete tumor cell elimination. Tumor regression was dependent on perforin, IFN-{gamma}, or TNF-{alpha}, because A9GP33 tumors developed in mice deficient in one of these genes. A9GP33 tumors arising in perforin- and IFN-{gamma}-deficient mice represented GP33 Ag-loss variants, demonstrating that GP33-specific CD8 T cells from these mice were able to exert an Ag selection pressure. In contrast, tumor cells growing in TNF-{alpha} knock-out mice still expressed the tumor-associated GP33 peptide despite the presence of activated GP33-specific CD8 T cells. These findings provide evidence for a crucial role of TNF-{alpha} in A9 tumor cell elimination by CD8 T cells in vivo.




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