NK cell phenotypes in Foxk1 deficient mice (82.13)

Abstract

Abstract Foxk1 is a member of the forkhead/winged-helix transcription factor family. Foxk1−/− mice have a gross deficit of natural killer (NK) cells, roughly three-fold, in the spleen, peripheral blood and bone marrow. Both mature and immature NK cells are lacking in the affected tissues. NK cells are the only major lymphocyte compartment affected. Bone marrow chimera experiments between Foxk1−/− and B6 (control) mice have shown that the defect is NK cell intrinsic. The remaining NK cells in Foxk1−/− are functionally defective directly ex vivo as determined by YAC-1 killing. However, following in vitro culture with either IL-2 or IL-15, the Foxk1−/− NK cells regain lytic function. To further analyze the cytotoxic defect of Foxk1−/− NK cells, we have examined the expression of components of the lytic pathway. Foxk1−/− NK cells express lower amounts of Perforin, but increased amounts of FasL, compared to B6 mice. These levels of cytotoxic effector molecules still do not provide us with an answer as to why Foxk1−/− NK cells have a defect in lytic function. To examine the NK cell number deficit in Foxk1−/− mice we have used flow cytometry to assess the various developmental stages of NK cells in Foxk1−/− and B6 mice and have found that Foxk1−/− mice had altered cell surface marker expression at the earliest progenitor stage. Gene expression profiles of early precursors from B6 and Foxk1−/− mice are being examined by microarray analysis.