Blood, 1 May 2002, Vol. 99, No. 9, pp. 3263-3271
IMMUNOBIOLOGY
Type I interferons produced by dendritic cells promote their
phenotypic and functional activation
Maria Montoya,
Giovanna Schiavoni,
Fabrizio Mattei,
Ion Gresser,
Filippo Belardelli,
Persephone Borrow, and
David F. Tough
From the Edward Jenner Institute for Vaccine Research,
Compton, Newbury, Berkshire, United Kingdom; Laboratory of Virology,
Istituto Superiore di Sanità, Rome, Italy; and INSERM
U255-Institut Curie, Paris, France.
Resting dendritic cells (DCs) are resident in most tissues and can
be activated by environmental stimuli to mature into potent antigen-presenting cells. One important stimulus for DC activation is
infection; DCs can be triggered through receptors that recognize microbial components directly or by contact with infection-induced cytokines. We show here that murine DCs undergo phenotypic maturation upon exposure to type I interferons (type I IFNs) in vivo or in vitro. Moreover, DCs either derived from bone marrow cells in vitro or
isolated from the spleens of normal animals express IFN-
and
IFN-
, suggesting that type I IFNs can act in an autocrine manner to
activate DCs. Consistent with this idea, the ability to respond to type
I IFN was required for the generation of fully activated DCs from bone
marrow precursors, as DCs derived from the bone marrow of mice lacking
a functional receptor for type I IFN had reduced expression of
costimulatory and adhesion molecules and a diminished ability to
stimulate naive T-cell proliferation compared with DCs derived from
control bone marrow. Furthermore, the addition of neutralizing
anti-IFN-/ antibody to purified splenic DCs in vitro
partially blocked the "spontaneous" activation of these
cells, inhibiting the up-regulation of costimulatory molecules,
secretion of IFN-
, and T-cell stimulatory activity. These results
show that DCs both secrete and respond to type I IFN, identifying type
I interferons as autocrine DC activators.
