Changes in Naive CD 4 T Cells

In the elderly, a dramatic shift within the CD4 + T cell population occurs, with an increased proportion having a memory phenotype with markedly decreased responsiveness. To determine what aspects o f the aged phenotype are dependent upon repeated contact with antigen in the environment, we examined CD4 + cells isolated from TC1L Tg n'nce. There is good evidence that no cross-reacting antigens for the Tg TCIL recognizing pigeon cytochrome c are found in the environment o f the animal, so that alterations in the Tg CD4 + cells with aging are likely to be due to antigen-independent processes. We found that in aged animals, TC1L transgeneP °' CD4 + cells, although decreased in number and antigen responsiveness, maintain a naive phenotype rather than acquinng a prototypxcal aged memory phenotype. In contrast, the population o f transgene 1 .. . . g CD4 + cells increase m proportion and express the aged phenotype. Consistent with their naive status, transgeneP °s cells o f aged individuals remain CD44 l° C D 4 5 R B h~, secrete IL-2 and not IL-4 or IFN-3, upon antigenic stimulation, and require costimulation to prohferate to anti-CD3 stimulation. These findings suggest that the aging-associated shift to CD4 cells expressing the memory phenotype is dependent on antigenic stimulation. However, the decrease in antigen responsiveness o f naive transgene p°~ cells, as revealed by a lower secretion o f IL-2 and IL-3 and a lower proliferative capacity, suggests that additional intrinsic changes occur with aging that do not depend on encounter with antigen.