MEL14+ CD4+ T-CELLS FROM AGED MICE DISPLAY FUNCTIONAL AND PHENOTYPIC CHARACTERISTICS OF MEMORY CELLS

Aging is accompanied by an increased fraction of memory CD4(+) T cells. Despite the fact that human memory cells have been reported to produce high levels of IL-2, studies in mice and man indicate an age-related decline in IL-2 production. In the present study, we examined whether these conflicting results depend on the activation pathway employed in a comparison of phenotypically distinct CD4(+) T cells from young and aged mice. Our data indicate an age-related decline in IL-2 production by CD4(+) T cells when the cells were stimulated with concanavalin A in the presence of accessory cells or the combination of immobilized anti-CD3 and soluble anti-CD28. However, when CD4(+) T cells were only stimulated with immobilized anti-CD3, an age-related increase in IL-2 production was observed. This age-related increase in IL-2 could be attributed to the ability of CD4(+) T cells from aged mice to produce IL-4 on this stimulation, since anti-IL-4 inhibited the IL-2 production in these cultures to levels found with cells from young mice. The addition of exogenous IL-4 greatly enhanced the IL-2 production of CD4(+) T cells from young mice to levels far beyond that of the aged counterparts, emphasizing the dominant role of IL-4 in the induction of IL-2 stimulated with immobilized anti-CD3. No differences were observed in the activation requirements of Mel14(-) CD4(+) T cells from young and aged mice. However, Mel14(+) CD4(+) T cells from aged mice were functionally and phenotypically more mature than their young counterparts, since they were capable of IL-2 and IL-4 production in response to anti-CD3 without the need of CD28 triggering and expressed Pgp-1 and ICAM-1 in a higher density. Our data indicate therefore that Mel14 is not a stable marker for naive CD4(+) T cells and might not be appropriate to distinguish these cells from memory cells.