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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] 

Abstract Previous work suggests that glucocorticoids upregulate expression of CD127, an IL-7 receptor component, on peripheral naïve T cells (NT), even though the total number of peripheral NT declines dramatically during malnourishment. We proposed that CD127 up-regulation contributes to peripheral NT reduction by increasing the scavenge rate of IL-7, providing a mechanism to rapidly adjust the total number of NTs during malnutrition. Each malnourished NT would then receive a larger dose of IL-7 than control NTs. We next wondered if this larger dose might confer additional energy-saving behaviors. NT migration across HEV’s may be a high energy-consuming activity. Thus, we compared lymph node entry rates of adoptively-transferred malnourished and control NT in malnourished and control recipients. Control CD4+ NTs migrated more efficiently than control CD8+ NT, but malnourished CD4+ and CD8+ NT migrated at equivalent rates, regardless of recipient diet. We next analyzed expression of proteins known to be involved in NT migration to uncover the currently unknown mechanisms responsible for these various migration patterns. Flow cytometry analysis revealed malnutrition significantly reduces expression of both components of LFA-1 (CD18 and CD11a), CD49d (a VLA-4 component), and S1PR1 in CD4+ and CD8+ NT. We also compared expression levels of ICAM-1 (CD54), a protein expressed in HEV’s which binds to LFA-1 on migrating NT, in malnourished and control lymph node tissue via confocal microscopy. Improved understanding of altered migration molecule expression during malnourishment should enhance our knowledge of the energy-conserving behavior of NT, as well as uncover strategies to improve vaccination responses in malnourished children.