Abstract

There has been increasing evidence that natural killer (NK) and killer (K) cell systems can play an important role in the first line of host defense mechanisms against neoplastic growth and metastasis as well as against viral, bacterial, and parasitic infections. Germfree, colostrum-deprived, immunologically """"""""virgin"""""""" piglets have absolutely no NK activity but have well-developed K cells mediating antibody-dependent cellular cytotoxicity (ADCC). Therefore, the gnotobiotic miniature swine model presents a unique opportunity for us to investigate the following four specific aims: (1) further definition of the cellular nature of porcine NK and K cells; (2) ontogenic development and differentiation of NK and K cells and their cell lineages; (3) nature of recognition receptors and/or function-associated surface structures of NK cells; and (4) regulation of NK cell activity in vitro and in vivo. Combinations of a short-term (2.5 to 4 hrs) ?51?Cr-release assay method for cytolytic effector activity of NK and K cells, a single cell in agarose assay method for target cell binding and cytolytic activity for a single or multiple targets, Percoll gradient fractionation of large granular lymphocytes, """"""""panning"""""""" and indirect rosette separation methods for NK and K cell separations and monospecific monoclonal antibodies produced by hybridoma technology, etc., will be used to characterize NK and K cells morphologically, immunologically, and functionally and to determine their cell lineages as well as to define the ontogeny, differentiation and activation, and/or regulatory mechanisms of these important host defense systems. This may eventually lead to manipulation or regulation of natural immunity against neoplastic diseases as well as microbial and parasitic diseases. (LB)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038336-02
Application #
3176412
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-02-15
Project End
1987-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Rosalind Franklin University of Medicine & Sci
Department
Type
Schools of Medicine
DUNS #
069501252
City
North Chicago
State
IL
Country
United States
Zip Code
60064