Protection against polyoma virus-induced tumors is perforin-independent.

Abstract

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.

• Authors: Anthony M Byers, Annette Hadley, Aron E Lukacher
• Journal: Virology (Virology) Vol. 358 Issue 2 Pg. 485-92 (Feb 20 2007) ISSN: 0042-6822 [Print] United States
• PMID: 17011010 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Membrane Glycoproteins
• Pore Forming Cytotoxic Proteins
• Tumor Necrosis Factor-alpha
• Perforin

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Cytokines (biosynthesis)
• Lymphocyte Count
• Membrane Glycoproteins (deficiency, genetics)
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL (genetics)
• Perforin
• Polyomavirus (immunology)
• Polyomavirus Infections (immunology)
• Pore Forming Cytotoxic Proteins (deficiency, genetics)
• Species Specificity
• Tumor Necrosis Factor-alpha (biosynthesis)
• Tumor Virus Infections (immunology)