Differential effects of chronic vitamin A status on the age-related changes in natural killer (NK) cell number and cytotoxic function

Aging and vitamin A (VA) deficiency have been associated with a reduction in the number and function of natural killer (NK) cells. However, the effect of marginal VA status or VA supplementation on these parameters during aging is unknown. To examine the interaction of VA status and age, we designed a 3 × 3 factorial study in which 144 male Lewis rats were fed a nutritionally adequate purified diet containing either 0.3 (marginal), 4.0 (control) or 50 (supplemented) μg retinol equivalents (as retinyl palmitate)/g of diet from the time of weaning until they were 2.5 (young), 8-10 (middle-aged) or 18-20 (old) months old. The number and percentage of NK cells (NKR-P1*) in peripheral blood mononuclear cells (PBMC) were determined by flow cytometry. NK cell cytotoxicity was determined using a ⁵¹Cr release assay. Both the number and percentage of NK cells in PBMC increased with age (P < 0.001 by 2-way ANOVA). Both the number and percentage of NK cells decreased, in all age groups, in rats with marginal VA status (P < 0.001) versus controls. Supplemental VA was associated with an increased number (in all age groups) and percentage of NK cells (in middle-aged and old) versus controls (P < 0.001). Both NK cell lytic activity (LA) (P = 0.003) and lytic efficiency (LE = LA/NK cell) (P < 0.001) decreased with age. VA status had no consistent effect on either NK cell LA or LE. PBMC in all age and diet groups were activated two to threefold after incubation with 500 U/ml IFNα for 1 h prior to assay. We conclude that, in this model, both age and VA status are important regulators of NK cell number. However, only age consistently affects NK cell cytotoxicity. (Supported by NIH AGO9839).