title: Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells.
abstract: Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.
authors: Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
authors: Smita S
authors: SS
authors: Iyer
authors: Janel Hart
authors: JH
authors: Chatraw
authors: Wendy G
authors: WG
authors: Tan
authors: E John
authors: EJ
authors: Wherry
authors: Todd C
authors: TC
authors: Becker
authors: Rafi
authors: R
authors: Ahmed
authors: Zoher F
authors: ZF
authors: Kapasi
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation; D004044:Dietary Proteins; D005260:Female; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011488:Protein Deficiency / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D004044:Dietary Proteins