dWe show here that mouse interferon-alpha (IFN-alpha)-producing cells (mIPC
s) are a unique subset of immature antigen-presenting cells (APCs) that sec
rete IFN-alpha upon stimulation with viruses.. mIPCs have a plasmacytoid mo
rphology, can be stained with an antibody to Ly6G and Ly6C (anti-Ly6G/C) an
d are Ly6C(+)B220(+)CDIIc(10)CD4(+); unlike other dendritic cell subsets, h
owever, they do not express CD8 alpha or CDIIb. Although mIPCs undergo apop
tosis in vitro, stimulation with viruses, IFN-alpha or CpG oligonucleotides
enhanced their survival and T cell stimulatory activity. In vivo, mIPCs we
re the main producers of IFN-alpha in cytomegalovirus-infected mice, as dep
letion of Ly6G(+)/C+ cells abrogated IFN-alpha production. mIPCs produced i
nterleukin 12 (IL-12) in response to viruses and CpG oligodeoxynucleotides,
but not bacterial products. Although different pathogens can selectively e
ngage various APC subsets for IL-12 production, IFN-alpha production is res
tricted to mIPCs' response to viral infection.