Glucocorticoids redirect naïve T cells to the bone marrow for preservation in malnourished mice 3187

Abstract Description Malnutrition is associated with reductions in the number and function of peripheral T cells. It is unknown whether malnourishment results in the increased apoptosis of naïve T cells or whether peripheral naïve T cells are directed to another lymphoid organ such as the bone marrow, which has been shown to be a protective environment in other contexts. Therefore, we evaluated the number of naïve T cells in the bone marrow and lymph nodes of malnourished and control mice. We found that malnourished mice demonstrated enhanced naïve T cell residency in the bone marrow and diminished T cell migration to the lymph nodes. Adoptive transfer studies revealed that malnutrition has intrinsic effects on naïve T cells; control naïve T cells entered the lymph nodes and spleen more efficiently than malnourished T cells regardless of the malnutrition status of the recipient, while malnourished naïve T cells entered the bone marrow more efficiently and experienced half as much cell death there as compared to control T cells, regardless of recipient. Experiments with mice conditionally deficient for the glucocorticoid receptor in T cells demonstrated that T cell sensitivity to glucocorticoids is required for malnutrition-induced T cell migration to the bone marrow. Overall, we have determined that excess glucocorticoids secreted during malnutrition redirect naïve T cells to the bone marrow where they experience less cell death. Funding Sources Supported by NSF/RUI 1951881; NSF/MRI 1920116. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)