Zinc, T-cell pathways, aging: role of metallothioneins

Zinc is an essential trace element for many biological functions, including immune functions. Indeed zinc is required for the biological activity of a thymic hormone, called thymulin in its zinc-bound form, important for the maturation and differentiation of T-cells. With advancing age zinc, thymic functions and peripheral immune efficiency show a progressive decline. Supp lementing zinc in old age restores them. Zinc is also relevant for liver ex trathymic T-cell pathway, being preeminent in old age. Since zinc is also r equired for metallothioneins (MTs) biological functions, binding zinc with high affinity, aim of the present article is to summarize findings from our laboratory regarding the role of zinc on T-cell pathways, investigating al so the possible cause of thymic involution and impaired liver extrathymic T -cell pathway in aging. Partial hepatectomy and liver regeneration are good models for this aim because of the likeness with aging for many immune fun ctions, including thymic functions. MTs levels are increased, other than in to the liver, also into the thymus during aging and in young hepatectomized (pHx) mice as compared to young sham controls. MTs may be one of the possi ble causes of reduced thymic efficiency and impaired liver extrathymic T-ce ll pathway in old age because of their higher zinc binding affinity rather than thymulin with consequent reduction of the free quota of zinc available for normal cell-mediated immunity. Following that, MTs may contribute to t hymic involution and impaired peripheral immune efficiency in aging and in young pHx mice with different roles during the whole life of an organism: p rotective in young-adult age which may became, at least, dangerous for immu ne responses in aging. In order to limit or avoid this latter MTs possible role in aging, supplementing physiological zinc may be useful to improve im mune responses in old age because of no interference of endogenous zinc on already high thymus MTs levels, but with caution for competition phenomena with copper, as documented in old mice and in syndrome of accelerate aging. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.