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Nutritional Immunology

Diminished Primary CD8 T Cell Response to Viral Infection during Protein Energy Malnutrition in Mice Is Due to Changes in Microenvironment and Low Numbers of Viral-Specific CD8 T Cell Precursors^1–3,

⁴ Department of Rehabilitation Medicine, Division of Physical Therapy, ⁵ Graduate Program in Nutrition Health Sciences, and ⁶ Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322

^* To whom correspondence should be addressed. E-mail: zkapasi{at}emory.edu.

Protein energy malnutrition (PEM) increases the incidence and severity of infection, causing morbidity and mortality in malnourished populations. Viral-specific cells are an important component of protective immunity. We hypothesized that reduction in the expansion of viral-specific cells and the microenvironment of the PEM host leads to increased incidence and severity of infections. We tested this hypothesis using a mouse model of lymphocytic choriomeningitis virus (LCMV) infection and an adoptive transfer system using P14 transgenic mice cells bearing T cell receptors specific for the D^b-restricted LCMV glycoprotein 33–41 epitope. We transferred equal numbers of P14 cells from mice fed either an adequate, 18% protein or low, 0.6% protein diet into C57BL/6 mice that had been fed adequate-protein (AP) or low-protein (LP) diets for 2 wk, infected them with LCMV, and followed them 1 wk postinfection. During PEM, the expansion of primary viral-specific CD8 T cells diminished; in LP diet-fed mice, it was only 2–3% of that in the AP diet-fed mice. Furthermore, the diminished primary CD8 T cell response during PEM may in part have been due to low numbers of viral-specific CD8 T cells and an altered microenvironment.