Chronic alcohol consumption perturbs the balance between thymus-derived and bone marrow-derived natural killer cells in the spleen.

Alcohol consumption reduces peripheral NK cell numbers and compromises NK cell cytolytic activity; however, the underlying mechanism is not understood completely. It was found recently that the peripheral NK cell pool consists largely of bone marrow (BM)-derived and thymus-derived cells, which are phenotypically and functionally different. The effects of alcohol consumption on these subpopulations have not been studied previously. Using a well-established alcohol-feeding model, we found that chronic alcohol consumption decreases the percentage and number of peripheral NK cells, especially those expressing a mature phenotype. Alcohol consumption did not alter NK cells in the thymus. NK cells in the BM were increased significantly; however, proliferation rate was not altered by alcohol consumption, which increased CD127+ and decreased Ly49D+ NK cells in the spleen but not in the BM. Chronic alcohol consumption increased IFN-gamma-producing NK cells and GATA-3 expression in splenic NK cells. Collectively, these results indicate that chronic alcohol consumption perturbs the balance between thymus-derived and BM-derived NK cells. The increased proportion of thymus-derived NK cells in the spleen likely results from impaired NK cell release from the BM.