Aging and human CD4(+) regulatory T cells.

Alterations in immunity that occur with aging likely contribute to the development of infection, malignancy and inflammatory diseases. Naturally occurring CD4(+) regulatory T cells (Treg) expressing high levels of CD25 and forkhead box P3 (FOXP3) are essential for regulating immune responses. Here we investigated the effect of aging on the number, phenotypes and function of CD4(+) Treg in humans. The frequency and phenotypic characteristics of CD4(+), FOXP3(+) T cells as well as their capacity to suppress inflammatory cytokine production and proliferation of CD4(+), CD25(-) T cells (target cells) were comparable in young (age or=65) individuals. However, when CD4(+), FOXP3(+) Treg and CD4(+), CD25(-) T cells were co-cultured at a ratio of 1:1, the production of anti-inflammatory cytokine IL-10 from CD4(+), CD25(-) T cells was more potently suppressed in the elderly than in the young. This finding was not due to changes in CTLA-4 expression or apoptosis of CD4(+), FOXP3(+) Treg and CD4(+), CD25(-) T cells. Taken together, our observations suggest that aging may affect the capacity of CD4(+), FOXP3(+) T cells in regulating IL-10 production from target CD4(+) T cells in humans although their other cellular characteristics remain unchanged.