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 functions against superinfecting agents and recall antigens, and this association is the major cause of the current high morbidity and mortality rate associated with measles virus (MV) infections. Dendritic cells (DCs) are antigen-presenting cells crucially involved in the initiation of primary and secondary immune responses, so we set out to define the interaction of MV with these cells. We found that both mature and precursor human DCs generated from peripheral blood monocytic cells express the major MV protein receptor CD46 and are highly susceptible to infection with both MV vaccine (ED) and wild-type (WTF) strains, albeit with different kinetics. Except for the down-regulation of CD46, the expression pattern of functionally important surface antigens on mature DCs was not markedly altered after MV infection. However, precursor DCs up-regulated HLA-DR, CD83, and CD86 within 24 h of WTF infection and 72 h after ED infection, indicating their functional maturation. In addition, 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 peripheral blood lymphocytes in vitro. These data indicate that the differentiation 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 proliferation and thus contribute to MV-induced immunosuppression.
Schnorr
J J
JJ
Institute for Virology and Immunobiology of the University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany.
Xanthakos
S
S
Keikavoussi
P
P
Kämpgen
E
E
ter Meulen
V
V
Schneider-Schaulies
S
S
D015703:Antigens, CD / Q000096:biosynthesis*; D051940:B7-2 Antigen; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008458:Measles Vaccine; D008459:Measles virus / Q000276:immunology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology / Q000821:virology; D011991:Receptors, Virus / Q000096:biosynthesis*; D015854:Up-Regulation; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D018664:Interleukin-12; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D000097802:CD83 Antigen; C497857:CD46 protein, human; C497964:CD86 protein, human