NUTRITION AND CELLULAR-IMMUNITY

We have investigated the influence of nutrition on immune function in animals and man over the past two decades. The profound impairment of immune function that had not been observed in children in developing countries could not consistently be reproduced in the laboratory setting; paradoxically, moderate nutritional restriction could even enhance T-cell-based cell-mediated immune responses in experimental animals. Studies of the crucial role of the element zinc in maintenance of vigorous cellular immunity provided at least a partial explanation of this paradox. Zinc, shown to be absolutely crucial for development and expression of both T- and B-cell functions, was commonly deficient as were other micronutrients under many conditions of protein-caloric malnutrition. Indeed, administration of adequate zinc alone could correct some of the T-cell-mediated immune functions in children with protein-calorie malnutrition. In later investigations we found that as long as all essential nutrients were supplied in adequate amounts, 40% chronic energy (calorie) restriction will regularly extend lifespan and maintain vigorous immunologic function while preventing numerous cancers and immunologically based diseases of aging, such as profound and destructive autoimmune diseases in genetically short-lived mice strains, as it was known to do for moderately long-lived rats and long-lived strains of mice. Such undernutrition without malnutrition appears to influence a wide range of critical metabolic and physiologic processes in both short-lived and long-lived animals. One of the most challenging of these influences was a down-regulation of cellular proliferation and cell turnover in each of the rapidly replicating tissues studied. It also regularly was possible to inhibit gene expression of certain oncogenic retroviruses, such as the mammary adenocarcinoma retrovirus, in highly susceptible strains of mice.