The defects in effector generation associated with aging can be reversed by addition of IL-2 but not other related γc-receptor binding cytokines

Aged naive CD4 T cells produce low levels of IL-2, leading to inefficient generation of effecters. The cells expand poorly, giving rise to few effecters with less activated phenotypes and reduced ability to produce cytokines. The aged cells also respond less vigorously in vivo. Addition of exogenous IL-2 or other gamma c receptor-signaling cytokines, restores expansion. However, only effectors generated in the presence of IL-2, are able to produce IL-2 in normal amounts and to become polarized to secrete Th2 cytokines. The defect in IL-2 production may be the only critical deficiency of aged naive CD4 T cells. Importantly, memory CD4 T cells generated from the IL-2 "restored" effecters are also deficient in IL-2 production, suggesting that a heritable change occurs during aging which effects production of IL-2 by resting naive and memory CD4 T cells, but not by optimally generated effecters. (C) 2000 Elsevier Science Ltd. All rights reserved.