Glucocorticoids intrinsically redirect naïve CD4+ T cells to the bone marrow for preservation in malnourished mice.

Abstract

Malnutrition impairs immunity and contributes significantly to child mortality. Among other immune changes during malnutrition, effector T cells experience a decline in number and function. As little is known about the effect of malnutrition on naïve T cells, we examined the impact of malnutrition on the naïve T-cell population. During malnutrition, the number of naïve T cells decreased in the lymph nodes and increased in the bone marrow, where naïve CD4+ T cells experienced less apoptosis than controls. An adoptive transfer experiment revealed that malnourished naïve CD4+ T cells preferentially migrated to the bone marrow, while ad libitum-fed control cells preferentially migrated to the lymph nodes in a T-cell-intrinsic fashion. Additionally, T-cell-specific lack of the glucocorticoid receptor greatly reduced the number of naïve T cells in the bone marrow of malnourished mice, while dexamethasone treatment elevated the number of naïve CD4+ T cells in the bone marrow. T-cell sensitivity to glucocorticoids was required for elevated expression of CXCR4 and CCR7 in naïve CD4+ T cells during malnutrition. Overall, naïve CD4+ T-cell migration to the bone marrow during malnutrition is intrinsic, requires sensitivity to glucocorticoids, and likely contributes to naïve T-cell preservation in mice.