NK Cells and gamma delta T Cells Mediate Resistance to Polyomavirus-Induced Tumors

NK and gamma delta 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+ alpha beta T cells are regarded as the main effectors in anti-tumor immunity. Here we report that adult TCR beta knockout (KO) mice that lack alpha beta but have gamma delta T cells remain tumor-free after PyV infection, whereas TCR beta 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 TCR beta x delta KO mice. These observations implicate gamma delta T and NK cells in the resistance to PyV-induced tumors. Cell lines established from PyV-induced tumors activate NK and gamma delta 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 gamma delta T cells against naturally occurring virus-induced tumors and suggest the involvement of NKG2D-mediated mechanisms.