Lymphocyte activation in human ageing: V. Acquisition of response to T cell growth factor and production of growth factors by mitogen-stimulated lymphocytes.

In order to ascertain why the T cell proliferative response declines with ageing, the age-related quality of the interleukin II (Il-2)-mediated signal during lymphocyte activation was investigated in mitogen-stimulated peripheral blood mononuclear cells (PBMC) from old (over 70 years) and adult (20-40 years) subjects. Both the Il-2 properties of supernatants produced by phytohaemagglutinin (PHA)-stimulated PBMC on Il-2 sensitive cells and the PHA-induced transformation in Il-2 sensitive T cells were decreased in the old subjects. Supplements with human Il-2 enhanced the DNA synthesis by PHA-, concanavalin-A-, or pokeweed-mitogen-activated lymphocytes in the two groups of subjects. The addition of Il-2 to old cultures restored a response similar to that observed in adults cells cultured without exogenous Il-2. The similarity of the dose-response curves to interleukin II indicated the unaltered affinity of the specific membrane receptors to the humoral factors. These findings strongly suggest that the immune deficiency commonly found in the elderly results principally from a selective alteration of the hormonal step of lymphocyte activation.