The effects of zinc deprivation upon the normal immunologic ontogeny of outbred N:NIH(S) mice was investigated by feeding lactating dams, from the day of parturition, and their pups to 8 weeks of age, a diet containing EDTA-washed isolated soy protein and 9 ppm (marginal zinc deficiency), 5 ppm (moderate zinc deficiency) or 2.5 ppm (severe zinc deficiency) zinc. Two groups of controls were provided with the same diet, but containing 100 ppm zinc; one group was fed ad libitum, the other was pair-fed to the level of food intake observed in the moderately deprived animals (5 ppm zinc). Severe growth retardation of lymphoid tissues, most notably thymus, was observed in all mice deprived of zinc. Indeed, the magnitude of splenic and thymic hypogenesis was directly dependent upon the severity of the dietary zinc deficit. Furthermore, zinc-deprived pups exhibited a significantly decreased splenic cellularity whether assessed per spleen or as a function of spleen weight, including a sharp reduction in both red and white cell counts. Similarly, at 4 weeks of age direct splenic plaque-forming cell responses to sheep erythrocyte immunization were dramatically diminished in mice that were moderately and severely deprived of zinc during the postnatal period. Finally, a striking and indicative feature of the critical import of zinc in immune maturation was the observation that these zinc-deficient mice at 4 weeks of age exhibited a highly disordered serum immunoglobulin profile, with absence of detectable IgM, IgG2a and IgA along with greatly elevated serum levels of IgG1. We suggest that deficiency of zinc during growth and development may predispose in a major way to acquired immune deficiency and opportunistic infection.
The influence of murine α-fetoprotein (AFP) on the threshold dose, mean tumor size, regression time, and number of progressors for Moloney sarcoma virus-(MSV) induced tumors in BALB/c mice was studied. AFP-treated mice developed larger tumors, required a longer period for regression, and had a significantly higher mortality. Furthermore, AFP, but not murine albumin or transferrin, allowed growth of tumors when normally subthreshold doses of virus were injected. These effects of AFP could be removed by pretreatment and precipitation of AFP by anti-AFP; on the other hand, they were not altered by dialysis and were noted at sera levels of approximately 170 to 440 µg/ml. The mechanism of this heightened susceptibility in AFP treated mice to MSV appears to be the generation of a cortisone, radiation sensitive splenic, and not lymph node, suppressor T cell. Indeed, the suppression produced by AFP was antigen nonspecific and could be demonstrated in unmanipulated mice after transfer of spleen cells from AFP-treated donors. This transfer of suppression was noted in IgG and IgA secondary responses to sheep red blood cells as well as by quantitating the response of T cell mitogens on spleen cells. These data suggest that AFP, in pharmacologic doses, either alters a subpopulation of spleen cells to exhibit suppressive function or else that AFP is involved in differential homing patterns of lymphoid cells. The relationships of AFP and immune competence appear broad and suggest the need for comparative studies with other oncofetal antigens.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.