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Background and aimApolipoprotein A1 (APOA1) deficiency is associated with severe reductions in plasma high density lipoprotein (HDL) cholesterol and therefore an increased atherosclerosis susceptibility. Although APOA1 can directly impact on inflammation and atherosclerosis, it can also suppress proliferation of hematopoietic stem cells and skew hematopoiesis, and thus alter immune cell numbers and function. In this study we aimed to dissociate the direct effects of APOA1 deficiency on immune cells in the context of atherosclerosis from effects that are generated through changes in bone marrow (BM) immune cell production. MethodsHematopoiesis was investigated in APOA1 knockout mice and wild-type controls. Furthermore, low density lipoprotein receptor (LDLR) knockout mice were transplanted with bone marrow from wild-type and APOA1 knockout mice and fed a Western-type diet to induce atherosclerosis.ResultsPlasma cholesterol levels and atherosclerotic plaque size and collagen content were unaltered upon reconstitution with BM from APOA1 knockout mice. However, APOA1 knockout BM recipients displayed lymphocytosis, and a strong increase in circulating CD4 T-cell numbers. This coincided with a strong increase in splenocyte numbers and a relative increase in splenic and circulating nau00efve T-cells. An increase in thymus size and thymic CCR9 expression suggested an increase in T-cell production, driven by an increase in hematopoietic stem cells and T lineage differentiation in the donor BM from APOA1 knockout mice.ConclusionsOur studies show that a genetic lack of APOA1 translated into long term changes in immune cell production from BM progenitors, leading to the development of nau00efve T-cells from the thymus, resulting in lymphocytosis. Furthermore, in accordance with a minor role for nau00efve T cells in atherogenesis, our studies suggest that the effect of APOA1 deficiency on BM does not underlie the diet-induced increase in atherosclerosis susceptibility associated with global APOA1 deficiency.