Circulating, interferon-producing plasmacytoid dendritic cells decline during human ageing

Increased frequency and severity of infections in the elderly have been taken as indicative of declining immune function. Dendritic cells (DCs), the most important antigen-presenting cells, play a central role in initiating and modulating immune responses. One type, DC2, arises from precursor plasmacytoid DCs (pDCs), a rare population of circulating blood cells, whose hallmark function is rapid and copious production of interferon-alpha (IFN-alpha) upon microbial challenge. We found significant decreases of the circulating pDCs during ageing in healthy adult humans, as defined both by flow cytometry and IFN-alpha generation. Mean pDC/mm3 in peripheral blood declined from 7.8 for the youngest age group (18-39 years) to 4.2 for the oldest (60-91 years; P = 0.017). IFN-alpha generation declined similarly, from 3537 to 1201 IU/ml, respectively (P = 0.006). There was also a slight decline over the age range in the amount of IFN generated per pDC (slope = -0.0087; P = 0.046). CD4+ T cells decreased by approximately 20% over the same age range (P = 0.001), while there was no change in the total lymphocyte or monocyte counts.