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From the * Institut National de la Santé et de la Recherche Médicale U 404 "Immunité et
Vaccination," Lyon, France; Measles causes a profound immune suppression which is responsible for the high morbidity and
mortality induced by secondary infections. Dendritic cells (DC) are professional antigen-presenting cells required for initiation of primary immune responses. To determine whether infection of DC by measles virus (MV) may play a role in virus-induced suppression of cell-mediated immunity, we examined the ability of CD1a+ DC derived from cord blood CD34+
progenitors and Langerhans cells isolated from human epidermis to support MV replication.
Here we show that both cultured CD1a+ DC and epidermal Langerhans cells can be infected
in vitro by both vaccine and wild type strains of MV. DC infection with MV resulted within
24-48 h in cell-cell fusion, cell surface expression of hemagglutinin, and virus budding associated with production of infectious virus. MV infection of DC completely abrogated the ability
of the cells to stimulate the proliferation of naive allogeneic CD4+ T cell as early as day 2 of
mixed leukocyte reaction (MLR) (i.e., on day 4 of DC infection). Mannose receptor-mediated
endocytosis and viability studies indicated that the loss of DC stimulatory function could not be
attributed to the death or apoptosis of DC. This total loss of DC stimulatory function required
viral replication in the DC since ultraviolet (UV)-inactivated MV or UV-treated supernatant
from MV-infected DC did not alter the allostimulatory capacity of DC. As few as 10 MV-
infected DC could block the stimulatory function of 104 uninfected DC. More importantly,
MV-infected DC, in which production of infectious virus was blocked by UV treatment or
paraformaldehyde fixation, actively suppressed allogeneic MLR upon transfer to uninfected
DC-T-cultures. Thus, the mechanisms which contribute to the loss of the allostimulatory
function of DC include both virus release and active suppression mediated by MV-infected
DC, independent of virus production. These data suggest that carriage of MV by DC may facilitate virus spreading to secondary lymphoid organs and that MV replication in DC may play
a central role in the general immune suppression observed during measles.
Centre National de la Recherche Scientifique Unité de Recherche
Associée 602, Lyon, France; § Schering-Plough Laboratory for Immunological Research, Dardilly,
France; and Baylor Institute of Immunology Research, Dallas, Texas 75246
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