Crucial role of TNF-alpha in CD8 T cell-mediated elimination of 3LL-A9 Lewis lung carcinoma cells in vivo
| Autor: | Evelyn Roth, Hanspeter Pircher, Felicia M. Rosenthal, Armelle Prévost-Blondel |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cytotoxicity
Immunologic Pore Forming Cytotoxic Proteins CD30 Immunology Epitopes T-Lymphocyte Mice Transgenic Biology CD8-Positive T-Lymphocytes Transfection Interleukin 21 Carcinoma Lewis Lung Interferon-gamma Mice Viral Proteins Cell Movement Tumor Cells Cultured Immunology and Allergy Cytotoxic T cell Animals Lymphocytic choriomeningitis virus IL-2 receptor Antigen-presenting cell Antigens Viral Glycoproteins Mice Knockout Membrane Glycoproteins Perforin Tumor Necrosis Factor-alpha ZAP70 Macrophages Lewis lung carcinoma Natural killer T cell Cytotoxicity Tests Immunologic Peptide Fragments Mice Inbred C57BL Cancer research Cell Division Neoplasm Transplantation |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 164(7) |
| ISSN: | 0022-1767 |
| Popis: | The role of perforin, IFN-γ, and TNF-α 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-γ, or TNF-α, because A9GP33 tumors developed in mice deficient in one of these genes. A9GP33 tumors arising in perforin- and IFN-γ-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-α 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-α in A9 tumor cell elimination by CD8 T cells in vivo. |
| Databáze: | OpenAIRE |
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