The effect of moderate protein malnutrition on murine T cell cytokine production

T cell responses and cytokine production requires recognition of antigenic peptides/MHC by the TCR/CD3 complex and reception of APC costimulatory signals through the CD28 counter-receptors. Protein malnutrition (PM) alters T cell immune responses and decreases resistance to infection. To determine the effect of PM on T cell cytokine production, interferon-γ (IFN)-γ, interleukin (IL)-2 and IL-4 production by splenic T cells from mice fed either a moderately protein deficient diet (4% casein) or a diet sufficient in protein (20% casein) in response to ConA or anti-CD3 was measured. The production of IL-4 was significantly decreased while production of IL-2 was increased from T cells of PM mice during co-culture with native APC. To determine the effect of PM on costimulatory and counter-receptor signals, T cells were stimulated with Concanavalin A (ConA) and costimulated with native APC, with APC from the reciprocal dietary group, or with antibody to CD28. APC from PM mice co-cultured with T cells of control mice retained a normal ability to costimulate control T cell cytokine production. However purified T cells from PM mice produced significantly less cytokines when co- cultured with control APC. In the absence of APC but in the presence of artificial costimulation by anti-CD28, the production of IL-2 and IL-4 from enriched T cells of PM mice was significantly decreased compared with T cells from control mice. Thus, the T cell counter-receptor pathway is significantly impaired, while APC costimulatory function remains normal, during PM.