Search for: All records

Abstract Glucocorticoids contribute to the daily migration patterns of T cells in well-nourished organisms and are elevated in the malnourished. We examined the effect of malnutrition on T cell migration by comparing the migration patterns of adoptively transferred malnourished and control T cells in the lymphoid organs of malnourished and control recipients. We found that malnourished T cells generally entered lymphoid tissues more efficiently than control T cells, regardless of recipient. Strikingly, the bone marrow of malnourished recipients attracted naïve malnourished T cells, but not control T cells, more efficiently than control bone marrow. In contrast, the spleens of malnourished and control mice attracted similar numbers of naïve T cells. Further experiments revealed that T cells residing in the bone marrow of malnourished mice express higher levels of CCR7 and lower levels of CD11a than control T cells. We also examined the effect of T cell-specific deficiency of the glucocorticoid receptor on T cell migration to the bone marrow in malnourished mice. Indeed, similarly low percentages of glucocorticoid receptor deficient T cells were observed in the bone marrow of malnourished and control mice, indicating that T cell expression of the glucocorticoid receptor is required for T cell migration to the bone marrow. Overall, we have determined that malnutrition modifies both the bone marrow and naïve T cells to promote naïve T cell migration to the bone marrow and that at least the T cell-specific effects are mediated via the glucocorticoid receptor. NSF-MRI [DBI- 1920116] NSF-RUI [IOS-1951881] 

Abstract Malnutrition is associated with reductions in the number and function of T lymphocytes. Previous studies in the lab suggest that malnutrition may also impart a “super-quiescent” phenotype to T cells, perhaps affecting the efficiency of their migration within and between lymph nodes. Thus, the purpose of this study is to evaluate the effect of malnutrition on T cell migration in vivo and to characterize malnutrition-induced changes in the expression of proteins known to be important for T cell migration. To determine if malnourishment alters T cell migration in vivo, we compared lymph node entry rates of adoptively-transferred malnourished and control T cells in malnourished and control recipients. In agreement with other studies, control CD4+ T cells were more efficient than control CD8+ T cells at entering the lymph nodes. Interestingly, regardless of recipient diet, malnourished CD4+ and CD8+ T cells entered the lymph nodes at equivalent rates, suggesting that malnourishment eliminates distinct lymph node entry efficiencies for CD8+ and CD4+ T cells. We also found important differences in the expression of key proteins involved in T cell migration between malnourished and control mice. Overall, we found that malnutrition disrupts T cell migration including the distinct migration efficiencies of CD4+ and CD8+ T cells. An improved understanding of T cell-intrinsic changes that occur during malnourishment should enhance our knowledge of CD4+ and CD8+ T cell migration and shed light on how organisms adapt to malnutrition. Supported by NSF-MRI [DBI- 1920116] NSF-RUI [IOS-1951881]