FROM NAIVE TO EFFECTOR - ALTERATIONS WITH AGING

We have used a T-cell receptor transgenic mouse model to study the rol e of antigen in the changes that occur as T cells age. We find that th e characteristic shift in the CD4 population to a predominance of memo ry phenotype T cells which accompanies aging in non-transgenic mice do es not occur, suggesting that this shift is a result of antigenic stim ulation. Thus at least one component of aging must be antigen dependen t. When responses of naive CD4 T cells from aged and young mice are di rectly compared in vitro, the former are relatively deficient in their ability to produce IL-2 and IL-3, they express altered levels of P-gl ycoprotein and they proliferate less well in the absence of exogenous cytokines. When the ability of both naive populations to generate effe ctors is compared, the number of effectors generated from aged naive c ells is much reduced and the effecters generated express lower levels of IL-2R alpha and produce reduced levels of cytokines. Importantly, a ddition of IL-2 restores proliferation of aged naive T cells, restores efficient effector generation and results in effecters seemingly indi stinguishable from chose derived from young CD4 cells. Similar phenoty pic and functional changes seen with aging are also found in T-cell po pulations from IL-2 and IL-2R alpha knockout mice. Thus the loss of op timal IL-2 production may participate in the aging process and may rep resent the main antigen-independent defect in the CD4 T-cell populatio n.