The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/9/801/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 6, September 15, 1997 801-812

Articles

Measles Virus Infects Human Dendritic Cells and Blocks Their Allostimulatory Properties for CD4+ T Cells

Isabelle Grosjean*, Christophe Caux§, Chantal Bella*, Ingrid Berger{ddagger}, Fabian Wild*, Jacques Banchereau§,||, and Dominique Kaiserlian*

From the * Institut National de la Santé et de la Recherche Médicale U 404 "Immunité et Vaccination," Lyon, France; {ddagger} 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

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.

Address correspondence to Dominique Kaiserlian, INSERM U404 Immunité et Vaccination, Ex-Batiment Institut Pasteur, Avenue Tony Garnier, 69365 LYON CX 07, France. Phone: 33-4-72-72-25-56; FAX: 33-4-72-72-25-67; E-mail: kaiserlian{at}lyon151.inserm.fr

1 Abbreviations used in this paper: DC, dendritic cells; HA, hemagglutinin; LC, Langerhans cells; LYS-1, wild-type MV strain; MOI, multiplicity of infection; MV, measles virus; PF, paraformaldehyde; PI, propidium iodide.


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