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Award ID contains: 1920116

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  1. 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] 
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  2. Abstract In mammals, T-cell migration is under circadian control, likely to anticipate daily rhythms in infection risk. Glucocorticoids are a major controller of circadian processes and malnutrition is associated with increased glucocorticoid secretion. Previous studies suggest malnutrition may impart a “super-quiescent” phenotype to T-cells, enabling a greater number of naïve T-cells to survive short-term malnutrition albeit with diminished function. Thus, we hypothesize that malnourished T-cells may conserve energy by disengaging from rhythmic migration under circadian control and/or foregoing migration to reside in the bone marrow instead. To test this hypothesis, the total number of nucleated cells and naïve CD4+ and CD8+ T-cells in the blood, spleen, bone marrow, and brachial and mesenteric lymph nodes were enumerated by flow cytometry every four hours over the course of one day from control and malnourished mice. Additionally, expression levels of CD127 and CXCR4 in both T-cell populations and the concentration of glucocorticoids in the blood were assessed. A better understanding of how malnutrition affects the circadian rhythm of T-cell migration will not only help identify the mechanisms of how circadian rhythms work, but also how organisms’ circadian rhythms change in response to malnutrition. This knowledge of how malnutrition disrupts the circadian rhythm of T-cells may help improve vaccination strategies in malnourished children. Supported by NSF-MRI [DBI- 1920116] NSF -RUI [IOS-1951881] 
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