- and CD8+ subclasses of dendritic cells undergo phenotypic and functional maturation in vitro and in vivo
* Department of Discovery Research, Immunex Corporation, Seattle, Washington; and
Institut de Biologie et de Médecine Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium
Correspondence: Thibaut De Smedt, Discovery Research Department, Immunex Corporation, 51 University Street, Seattle, WA 98101. E-mail: desmedtt{at}immunex.com
Dendritic cells (DCs) are essential for the priming of immune
responses. This antigen-presenting function of DCs develops in sequence
in a process called maturation, during which they become potent
sensitizers of naïve T cells but reduce their ability to
capture and process antigens. Some heterogeneity exists in mouse-DC
populations, and two distinct subsets of DCs expressing high levels of
CD11c can be identified on the basis of CD8
expression. We have
studied the phenotype and maturation state of mouse splenic
CD8- and CD8+ DCs. Both subsets were
found to reside in the spleen as immature cells and to undergo a
phenotypic maturation upon culture in vitro in
GM-CSF-containing medium or in vivo in response to
lipopolysaccharide. In vitro and in vivo
analyses showed that this maturation process is an absolute requisite
for DCs to acquire their T-cell priming capacity, transforming
CD8- and CD8+ DCs into potent and
equally efficient activators of naïve CD4+ and
CD8+ T cells. Furthermore, these results highlight the
importance that environmental factors may have on the ability of DC
subsets to influence Th responses qualitatively; i.e., the ability to
drive Th1 versus Th2 differentiation may not be fixed immutably for
each DC subset.
Key Words: CD4+/CD8+ • T-cell activation • GM-CSF • lipopolysaccharide
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