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Department of Nutrition and * Graduate Program in Nutrition, The Pennsylvania State University, University Park, PA 16802
3To whom correspondence should be addressed.
Natural killer (NK) cells function in the regulation of immune
responses and in the surveillance of malignant or other abnormal cells.
Little is known of the effects of chronic marginal vitamin A (VA)
status or VA supplementation, or their interaction with age, on NK cell
number and cytolytic activity. We have conducted a two-factor
(diet, age) study in which male Lewis rats were fed AIN-93M diet,
modified to contain either 0.3 (designated marginal), 4.0 (control) or
50 (supplemented) mg retinol equivalents (RE)/kg diet, from the time of
weaning until the ages of 2.5 mo (young), 810 mo (middle-aged) or
1820 mo (old). Natural killer cells were identified and quantified in
peripheral blood mononuclear cells (PBMC) and spleen with the use of
flow cytometry, and NK cell cytotoxicity was assayed. The number and
percentage of PBMC NK cells increased with age (P
< 0.0001 by two-way ANOVA). For all age groups, values were
lowest in rats with marginal VA status (P < 0.0001
vs. controls). NK cell lytic activity also declined with age
(P = 0.0003). As a result, NK cell lytic efficiency
(lytic activity per NK cell) decreased markedly with age
(P < 0.0001). Regardless of the donor's age or VA
status, PBMC NK cell cytotoxicity doubled (100 ± 25% increase)
after exposure to interferon-
(5 x 105
U/L for 1 h before assay), indicating that
IFN-stimulated lytic activity was related directly to basal NK cell
activity. If the relationships observed in this animal model can be
applied to humans, these data suggest that elderly people consuming
diets chronically low in VA may be at increased risk for infectious or
neoplastic diseases.
KEY WORDS: aging immunophenotyping vitamin A supplementation liver function rats
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