Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.

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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-a (IFN-a) 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-a generation. Mean pDC/mm 3 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-a 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 À0.0087; P 0.046). CD4T 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.