Chronic marginal vitamin A status affects the distribution and function ofT cells and natural T cells in aging Lewis rats

Although both vitamin A (VA) deficiency and aging are independently associa ted with alterations in immune function, the effects of marginal VA status or VA supplementation on the immune system during aging were not studied. A long-term dietary study was conducted in a rat model of aging to quantify changes in T-cell populations in blood and spleen, including T-cells bearin g a marker of natural killer (NKT) cells. The study included nine treatment groups [three levels of dietary VA: marginal (0.35 RE/kg diet), control (4 .0 RVkg diet), and supplemented (50 RE/kg diet); and three age groups: youn g (2-3 mo), middle-aged (8-10 mo), and old 20-22 mo); diets were fed contin uously from weaning to the end of the study period. CD3(+)/CD4(+) T-cells d ecreased in percentage and number in blood with age, CD8(+) cells increased (%), and the CD4/CD8 ratio decreased. Conversely, aging was associated wit h increased NKT cells (phenotype CD3(intermediate)/NKR-P1(+)). Based on reg ression analysis of flow cytometry data, the phenotype of most NKT cells wa s CD3(intermediate)/NKR-P1(+)/CD28(-). NKT cells, which are most likely of extrathymic origin, accounted for most of the decrease in the CD4/CD8 ratio . Marginal VA status, particularly in older rats, was associated with incre ases in the percentage of CD8(+) T cells, percentage and number of NKT cell s, and peripheral blood cell anti-CD3 epsilon-stimulated proliferative resp onse, and decreases in the CD4/CD8 T-cell ratio and splenic cell interleuki n-2 production. These differences and the reciprocal changes observed for N KT cells vs, T- and classical NK cells in aging VA-marginal rats suggest th at low VA status during aging may increase the risk of infectious or neopla stic diseases that require a normal balance of T-cell or NK-cell responses.