Interleukin 2, but not other common γ chain-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice

Development of effecters from naive CD4 cells occurs in two stages. The early stage involves activation and limited proliferation in response to T cell receptor (TCR) stimulation by antigen and costimulatory antigen presenting cells, whereas the later stage involves proliferation and differentiation in response to growth factors. Using a TCR-transgenic (Tg(+)) model, we have examined the effect of aging on effector generation and studied the ability of gamma c signaling cytokines to reverse this effect. Our results indicate that responding naive CD4 cells from aged mice, compared with cells from young mice, make less interleukin (IL)-2, expand poorly between days 3 to 5, and give rise to fewer effecters with a less activated phenotype and reduced ability to produce cytokines. When exogenous IL-2 or other gamma c signaling cytokines are added during effector generation, the Tg(+) cells from both young and aged mice proliferate vigorously. However, IL-4, IL-7, and IL-15 all fail to restore efficient effector production. Only effecters from aged mice generated in the presence of IL-2 are able to produce IL-2 in amounts equivalent to those produced by effecters generated from young mice, suggesting that the effect of aging on IL-2 production is reversible only in the presence of exogenous IL-2.