Aged mice exhibit increased frequencies of CD4+ T cells with a regulatory phenotype (85.20)

Abstract

Abstract In vivo, age-related defects in CD4+ T cell function lead to reduced expansion, IL-2 production, NF-κB activation and B cell helper activity. These defects are significant as they result in reduced vaccine efficacy in the elderly. To date, relatively little is known about what factors contribute to these age-related defects in vivo. By using real time-PCR (RT-PCR) and intracellular flow cytometry, we have identified candidate cell subsets and molecules that may contribute to the observed immunosuppression. Spleens of young (4 months) and aged (24 months) mice displayed significantly higher expression of interleukin-10 (IL-10) as determined by RT-PCR. Analysis of cell subsets isolated by sorting revealed a significant increase in IL-10 expression in aged CD4+ T cells compared to young. Following intracellular cytokine staining, a statistically significant increase in CD4+IL-10+ cells (~15 fold) was observed in aged (26 months) compared to young (2 months) mice. Aged CD4+ T cells exhibited significantly higher expression of CD25 (~3 fold), GITR (~5 fold) and CTLA-4 (~4 fold) compared to young CD4+ T cells, as well as greater overall numbers of cells expressing each marker. Following intracellular staining, both intact and transgenic CD4+ T cell populations in aged mice displayed greater numbers of Foxp3-expressing cells compared to young populations. Our results demonstrate that in aged mice, several molecules and cells associated with immune regulation are present in significantly higher amounts than in young mice and that future experiments are required to determine the effects of these elements on naïve CD4+ T cell and aged immune responses. This research was supported by NIH grants AG02160 and AG21054.