Abstract

We have shown that virus infections and interferon inducers stimulate natural killer (NK) cell activation, proliferation and accumulation in target organs such as liver, lung, and peritoneum. Also stimulated by viruses are cytotoxic T cells which may, like NK cells, have a large granular lymphocyte (LGL) morphology. A subclass of stimulated T cells is allospecific whereas others are virus-specific. We propose to examine NK/LGL and T/LGL accumulation in organs during infection or IFN stimulus, to determine whether this accumulation is due to chemotaxis or to in situ differentiation or proliferation, and to determine which organs (spleen or bone marrow) are the source of NK cells appearing in target organs. Rat and hamster monoclonal antibodies to mouse NK cells will be made from animals stimulated with an NK cell clone or purified mouse blast NK/LGL. These antibodies, as well as others already available, will be used to phenotype NK cells in different organs and at different stages of activation, to compare them with T/LGL, and to localize NK cells in organs by immunohistochemistry. The antibodies will also be used to define cell receptors involved in chemotaxis. The proposed experiments should help elucidate how NK cells respond to stimuli within an infected animal, such that they may effectively contribute to natural immunity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034461-09
Application #
3172167
Study Section
Experimental Immunology Study Section (EI)
Project Start
1983-05-01
Project End
1995-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Waggoner, Stephen N; Daniels, Keith A; Welsh, Raymond M (2014) Therapeutic depletion of natural killer cells controls persistent infection. J Virol 88:1953-60
Mishra, Rabinarayan; Welsh, Raymond; Szomolanyi-Tsuda, Eva (2014) NK cells and virus-related cancers. Crit Rev Oncog 19:107-19
Rodriguez, Idalia A; Welsh, Raymond M (2013) Possible role of a cell surface carbohydrate in evolution of resistance to viral infections in old world primates. J Virol 87:8317-26
Welsh, Raymond M; Waggoner, Stephen N (2013) NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections. Virology 435:37-45
Cornberg, Markus; Kenney, Laurie L; Chen, Alex T et al. (2013) Clonal exhaustion as a mechanism to protect against severe immunopathology and death from an overwhelming CD8 T cell response. Front Immunol 4:475
Waggoner, Stephen N; Cornberg, Markus; Selin, Liisa K et al. (2012) Natural killer cells act as rheostats modulating antiviral T cells. Nature 481:394-8
Waggoner, Stephen N; Taniguchi, Ruth T; Mathew, Porunelloor A et al. (2010) Absence of mouse 2B4 promotes NK cell-mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis. J Clin Invest 120:1925-38
Mishra, Rabinarayan; Chen, Alex T; Welsh, Raymond M et al. (2010) NK cells and gammadelta T cells mediate resistance to polyomavirus-induced tumors. PLoS Pathog 6:e1000924
Rathinam, Vijay A K; Jiang, Zhaozhao; Waggoner, Stephen N et al. (2010) The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol 11:395-402
Mathurin, Keisha S; Martens, Gregory W; Kornfeld, Hardy et al. (2009) CD4 T-cell-mediated heterologous immunity between mycobacteria and poxviruses. J Virol 83:3528-39

Showing the most recent 10 out of 77 publications