Age-dependent modifications of Type 1 and Type 2 cytokines within virgin, and memory CD4+ T cells in humans

Several alterations in immune function and a concomitant progressive increase in pro-inflammatory status are the major characteristics of ageing process. Cytokines play a key role during ageing acting both in regulatory communication among cells and in effector activity during an immune response. The impact of age on intracellular Type 1 (IFN-gamma and TNF-alpha) and Type 2 (IL-4) cytokines, after stimulation with PMA/ionomycin, was determined in three CD4(+) T subsets, i.e. CD95(-)CD28(+) (virgin), CD95(+)CD28(+) (activated/memory), and CD95(+)CD28(-) (effector/memory) from 47 subjects aged between 21 and 99 years. The percentage of IFN-gamma positive cells significantly decreased in virgin CD4(+) subset both in old and nonagenarian subjects, as well as in activated/memory T cells from old in comparison with young subjects. The percentage of TNF-alpha positive cells significantly decreased in activated/memory CD4(+) subset from old people. Regarding Type 2 cytokines, IL-4 positive cells significantly increased in activated/memory CD4(+) subset from nonagenarians. On the whole our data indicate that: (1) different Type I and Type 2 cytokine-positive CD4(+) T subsets are differently affected by ageing process; (2) activated/memory T cells appear to be the most affected subset; (3) a shift towards an increased role of Type 2 cytokines and a diminished role of Type I cytokines emerges with ageing. (c) 2006 Elsevier Ireland Ltd. All rights reserved.