Protection against polyoma virus-induced tumors is perforin-independent.
CD8 T cells are necessary for controlling tumors induced by mouse polyoma virus (PyV), but the effector mechanism(s) responsible have not been determined. We examined the PyV tumorigenicity in C57BL/6 mice mutated in Fas or carrying targeted disruptions in the perforin gene or in both TNF receptor type I and type II genes. Surprisingly, none of these mice developed tumors. Perforin/Fas double-deficient radiation bone marrow chimeric mice were also resistant to PyV-induced tumors. Anti-PyV CD8 T cells in perforin-deficient mice were found not to differ from wild type mice with respect to phenotype, capacity to produce cytokines or maintenance of memory T cells, indicating that perforin does not modulate the PyV-specific CD8 T cell response. In addition, virus was cleared and persisted to similar extents in wild type and perforin-deficient mice. In summary, perforin/granzyme exocytosis is not an essential effector pathway for protection against PyV infection or tumorigenesis.
Byers
Anthony M
AM
Department of Pathology, Emory University School of Medicine, Woodruff Memorial Research Building, Rm. 7307, 101 Woodruff Circle, Atlanta, GA 30322, USA.
Hadley
Annette
A
Lukacher
Aron E
AE
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL / Q000235:genetics; D054353:Perforin; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000172:deficiency / Q000235:genetics; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014412:Tumor Virus Infections / Q000276:immunology*
D016207:Cytokines; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin