INDUCTION OF MATURATION OF HUMAN BLOOD DENDRITIC CELL PRECURSORS BY MEASLES-VIRUS IS ASSOCIATED WITH IMMUNOSUPPRESSION

As well as inducing a protective immune response against reinfection, acute measles is associated with a marked suppression of immune functi ons against superinfecting agents and recall antigens, and this associ ation is the major cause of the current high morbidity and mortality r ate associated with measles virus (MV) infections, Dendritic cells (DC s) are antigen-presenting cells crucially involved in the initiation o f primary and secondary immune responses, so we set out to define the interaction of MV with these cells, We found that both mature and prec ursor human DCs generated from peripheral blood monocytic cells expres s the major MV protein receptor CD46 and are highly susceptible to inf ection with both MV vaccine (ED) and wild-type (WTF) strains, albeit w ith different kinetics. Except for the down-regulation of CD46, the ex pression pattern of functionally important surface antigens on mature DCs was not markedly altered after MV infection, However, precursor DC s up-regulated HLA-DR, CD83, and CD86 within 24 h of WTF infection and 72 h after ED infection, indicating their functional maturation, In a ddition, interleukin 12 synthesis was markedly enhanced after both ED and WTF infection in DCs, On the other hand, MV-infected DCs strongly interfered with mitogen-dependent proliferation of freshly isolated pe ripheral blood lymphocytes in vitro. These data indicate that the diff erentiation of effector functions of DCs is not impaired but rather is stimulated by MV infection, Yet, mature, activated DCs expressing MV surface antigens do give a negative signal to inhibit lymphocyte proli feration and thus contribute to MV-induced immunosuppression.