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NK cells and gammadelta T cells mediate resistance to polyomavirus-induced tumors

Rabinarayan Mishra1, Alex T Chen, Raymond M Welsh

  • 1Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Plos Pathogens
|June 5, 2010
PubMed

Insights

Natural killer (NK) and gammadelta T cells protect against polyomavirus-induced tumors in mice. These immune cells, along with NKG2D signaling, are crucial for preventing viral tumor development.

Area of Science:

  • Immunology
  • Virology
  • Oncology

Background:

  • Natural killer (NK) and gammadelta T cells are known to eliminate tumor cells in experimental models.
  • The role of these cells in controlling virus-induced tumors in vivo remains unclear.
  • CD8+ alphabeta T cells are traditionally considered the primary mediators of anti-tumor immunity.

Purpose of the Study:

  • To investigate the role of gammadelta T cells and NK cells in resistance to polyomavirus (PyV)-induced tumors.
  • To elucidate the mechanisms underlying the anti-tumor activity of these immune cells against PyV.

Main Methods:

  • Utilized T-cell receptor beta (TCRbeta) knockout (KO) mice, TCRbeta x delta KO mice, and E26 mice (lacking NK and T cells) to study PyV infection.
  • Established and analyzed cell lines from PyV-induced tumors.
  • Assessed NK and gammadelta T cell activation and cytotoxicity in vitro and in vivo.
  • Investigated the role of NKG2D ligand Rae-1 and NKG2D-blocking antibodies.

Main Results:

  • TCRbeta KO mice (with gammadelta T cells) remained tumor-free after PyV infection, while TCRbeta x delta KO mice (lacking all T cells) developed tumors.
  • E26 mice (lacking NK and T cells) developed tumors earlier than TCRbeta x delta KO mice, implicating NK cells.
  • PyV tumor cells expressed Rae-1, activated NK and gammadelta T cells, and were susceptible to NK cell-mediated killing, which was blocked by anti-NKG2D antibodies.

Conclusions:

  • NK and gammadelta T cells play a significant protective role against naturally occurring virus-induced tumors.
  • NKG2D-mediated mechanisms are involved in the anti-tumor activity of NK and gammadelta T cells against PyV.
  • These findings highlight the importance of innate and gammadelta T-cell immunity in controlling viral oncogenesis.

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