Macrophage-mediated depression of T-cell proliferation in zinc-deficient mice.

Splenic T-cells and macrophages (adherent cells) from zinc-deficient (ZD) mice and pair-fed (PF) control mice were isolated, purified and recombined in defined proportions to evaluate the contribution of each cell type to impaired mitogenesis. The results of cell crossover experiments revealed that the observed depression in T-cell proliferation in the ZD mice was indirect and due to a primary defect in the macrophage population that could be overcome by increasing the proportion of macrophages in culture. In contrast, the proliferative capacity of purified T-cells from ZD mice was not different from control levels when the cells were combined with macrophages from PF control mice. Similar results were obtained in neonatally thymectomized ZD and PF mice, suggesting that long-lived T-cells may have been processed normally through the thymus before the 6 wk of dietary zinc deprivation. After 12 wk of zinc depletion, however, the proliferative capacity of T-cells from ZD mice was significantly depressed, suggesting a direct effect on the maintenance or maturational state of T-cell subpopulations when the period of deficiency approached the half-life of these cells. These results emphasize the continuum of immunologic alteration with progressive nutritional intervention, which may vary depending on the age of induction and the duration of depletion.