Department of Pathology
Age Factors; Animals; Cell Line, Tumor; *Killer Cells, Natural; Mice; Mice, Inbred C57BL; Mice, Knockout; NK Cell Lectin-Like Receptor Subfamily K; Nuclear Matrix-Associated Proteins; Nucleocytoplasmic Transport Proteins; Polyomavirus; Polyomavirus Infections; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; *Salivary Gland Neoplasms; *T-Lymphocytes; Tumor Virus Infections; Viral Load
Cancer Biology | Life Sciences | Medicine and Health Sciences | Pathology
NK and gammadelta T cells can eliminate tumor cells in many experimental models, but their effect on the development of tumors caused by virus infections in vivo is not known. Polyomavirus (PyV) induces tumors in neonatally infected mice of susceptible strains and in adult mice with certain immune deficiencies, and CD8+ alphabeta T cells are regarded as the main effectors in anti-tumor immunity. Here we report that adult TCRbeta knockout (KO) mice that lack alphabeta but have gammadelta T cells remain tumor-free after PyV infection, whereas TCRbeta x delta KO mice that lack all T cells develop tumors. In addition, E26 mice, which lack NK and T cells, develop the tumors earlier than TCRbeta x delta KO mice. These observations implicate gammadelta T and NK cells in the resistance to PyV-induced tumors. Cell lines established from PyV-induced tumors activate NK and gammadelta T cells both in culture and in vivo and express Rae-1, an NKG2D ligand. Moreover, these PyV tumor cells are killed by NK cells in vitro, and this cytotoxicity is prevented by treatment with NKG2D-blocking antibodies. Our findings demonstrate a protective role for NK and gammadelta T cells against naturally occurring virus-induced tumors and suggest the involvement of NKG2D-mediated mechanisms.
Rights and Permissions
Copyright: © 2010 Mishra et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Mishra R, Chen AT, Welsh RM, Szomolanyi-Tsuda E (2010) NK Cells and γδ T Cells Mediate Resistance to Polyomavirus–Induced Tumors. PLoS Pathog 6(5): e1000924. doi:10.1371/journal.ppat.1000924. Link to article on publisher's site
Mishra, Rabinarayan; Chen, Alex T.; Welsh, Raymond M.; and Szomolanyi-Tsuda, Eva, "NK cells and gammadelta T cells mediate resistance to polyomavirus-induced tumors" (2010). Open Access Articles. 2365.