Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Microbiology and Immunology

Natural Killer cells (NK) are groups of large granular lymphocytes belonging to the innate immune system, with different phenotype, distribution, and function. These cells display a unique powerful non-specific cytotoxic activity against virally infected cells and tumors. They arise from common lymphoid progenitors in the bone marrow of mice and humans. Although NK cells have been well studied, the full pathway of their development and commitment is not fully dissected. Comprehensively understanding how NK cells are derived and estimating their kinetics in tissues will facilitate the development of targeted therapies to boost NK cells function for patients with cancer, human immunodeficiency virus or hepatitis C virus infections. Albeit, evaluating dynamics of lymphocytes in tissues proved difficult and there are striking differences in life span estimates of human and mouse lymphocytes. Many labeling agents have been used to evaluate kinetics of lymphocytes such as 5-bromo-2'-deoxyuridine (5-BrdU) and the stable isotope deuterium, yet little is known about half lives of NK cells in tissues. Here, we used the Id2CreErt2Rosa26RYFP/YFP mouse model to estimate the half life of different stages and phenotypes of NK cells in different organs; bone marrow, liver and spleen. The Id2CreErt2Rosa26RYFP/YFP system allows the expression of YFP reporter protein in the expense of conditional deletion of the Id2 (inhibitor of DNA binding 2) using a tamoxifen-induced promotor. Our studies show that the TRAIL+ NK cells displayed the longest half life (about 7 weeks), which is double that of DX5+NK cells in liver-about 3 weeks

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