Cell-Mediated Effector Mechanisms in Aging Humans

Abstract

Specific and nonspecific cell-mediated effector mechanisms have been simultaneously assayed in 15 aged humans. 8 were female and 7 male, including a 114-year-old male in remarkably good health. Proliferative response to alloantigens, the generation of T killer cells and the ability to express cell-mediated lympholysis as well as the presence of natural cell-mediated cytotoxicity against K562 tumor cell line and the capacity to mount an ADCC response to RhD+ human red blood cell sensitized with anti-D antisera, revealed that in the human aged, while T function significantly declines, nonspecific cell-mediated effector mechanisms are operative.

The Immune Status of Healthy Centenarians

“…The immunocompetence of aging experimental animals and humans has been studied by many investigators 3–25 . Although there are significant changes in other components of the immune system (see below), the major defects appear to arise in the T‐lymphocyte population 10,14,16–20 . The total number of these cells in the peripheral blood does not change appreciably with age, but the subsets of T‐lymphocyte populations undergo dramatic changes.…”

Proliferative Response in Solid Culture of T Cells from Healthy Aged Subjects

“…Impaired proliferative and effector T-cell responses have been linked to the process of aging [16,25]. There is evidence that reduc tion in the size of the T-cell pool [8] and alter ation in the mechanisms that initiate T-cell activation or a reduction in the intrinsic ca pacity of individual T cells to enter into cell cycle, may account for the observed T-cell dysfunction [20].…”

“…One of the most significant altera tions is related to a decline in T-cell function [24] accompanied by a disturbance of the Tlymphocyte pool [8,13], reduced prolifera tive responses to plant lectins and in both allogenic and autologous reactions [10,12,14] as well as in the generation of Con-Astimulated T-suppresor cells [15]. Further more, our laboratory has reported a signifi cant impairment of the generation of cyto toxic T cells and in the expression of cellmediated lympholysis during immunosenescence [25]. The poor proliferative response of T cells in the aged has been attributed to a decrease of responding cells entering the cell cycle along with a reduction in the ability to divide and expand [17], On the other hand, the function of accessory cells and the num ber of monocytes seems to remain intact [18,26], In the present investigation, we have evaluated the response of aged lymphocytes in solid cultures in which direct intercellular contact is prevented.…”