AbstractThe ability of CD4+ T cells from CBA/Rij mice to produce interleukin (IL) 2 after stimulation with anti‐CD3, concanavalin A, or the combination of phorbol 12‐myristate 13‐acetate and ionomycin declines during aging. This phenomenon was accompanied by an increased production of IL 4 and interferon‐γ. These age‐related changes in lymphokine production correlated with the decrease in the percentage of CD45RBhi CD4+ T cells from about 80% in 2‐month‐old to about 40% in 27‐month‐old mice. This phenotypic shift was responsible for the decline in IL 2 production, because in young and in old mice CD45RBhi CD4+ T cells were more potent IL 2 producers than CD45RBlo cells. Moreover, old CD45RBhi CD4+ T cells produced less IL 2 than their young counterparts. Proliferative responses by T cells from old mice were lower than those of young mice, regardless whether the cultures were supplemented with IL 2, IL 4 or both lymphokines. As far as CD4+ T cells were concerned, this hyporesponsiveness was found in the CD45RBlo as well as in the CD45RBhi CD4+ T cell population.