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: Smita S Iyer, Janel Hart Chatraw, Wendy G Tan, E John Wherry, Todd C Becker, Rafi Ahmed, Zoher F Kapasi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 1 Pg. 77-84 (Jan 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22116826 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Dietary Proteins

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, pathology, virology)
• Cell Proliferation
• Dietary Proteins
• Female
• Immunologic Memory
• Lymphocytic Choriomeningitis (immunology, pathology, virology)
• Lymphocytic choriomeningitis virus (immunology)
• Mice
• Mice, Transgenic
• Protein Deficiency (genetics, immunology, pathology, virology)