Distinct lymph node entry efficiencies for CD8+ and CD4+ T cells are eliminated during malnourishment.

Abstract

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.