Measles Virus Suppresses Cell-mediated Immunity by Interfering with the Survival and Functions of Dendritic and T Cells

Abstract

Secondary infections due to a marked immunosuppression have long been recognized as a major cause of the high morbidity and mortality rate associated with acute measles. The mechanisms underlying the inhibition of cell-mediated immunity are not clearly understood but dysfunctions of monocytes as antigen-presenting cells (APC) are implicated. In this report, we demonstrate that measles virus (MV) replicates weakly in the resting dendritic cells (DC) as in lipopolysaccharide-activated monocytes, but intensively in CD40-activated DC. The interaction of MV-infected DC with T cells not only induces syncytia formation where MV undergoes massive replication, but also leads to an impairment of DC and T cell function and cell death. CD40-activated DC decrease their capacity to produce interleukin (IL) 12, and T cells are unable to proliferate in response to MV-infected DC stimulation. A massive apoptosis of both DC and T cells is observed in the MV pulsed DC–T cell cocultures. This study suggests that DC represent a major target of MV. The enhanced MV replication during DC–T cell interaction, leading to an IL-12 production decrease and the deletion of DC and T cells, may be the essential mechanism of immunosuppression induced by MV.

Poxvirus as a vector to transduce human dendritic cells for immunotherapy: abortive infection but reduced APC function

“…This is comparable with the resistance of mature DC to influenza virus infections, 30 but is in contrast to measles virus, which replicates in immature and even more efficiently in mature DC. 31,32 The cytokines IL-4 and GM-CSF added to immature and mature DC are not known to have antiviral effects. Possibly, the DC derived from blood monocytes as used here retained their non-permissive phenotype that has been described for VV infected blood monocytes/macrophages.…”

“…Interference with mature DC functions has also been described for measles virus. 31,32 However, in contrast to the measles virus, VV infection of DC is abortive. This excludes secondary VV infection of T cells as the cause of a reduced proliferative response in MLR.…”

Characterization of novel safe lentiviral vectors derived from simian immunodeficiency virus (SIVmac251) that efficiently transduce mature human dendritic cells

“…64 After 6 days of culture in the presence of 50 ng/ml hrGM-CSF and 500 U/ml hrIL-4 (kindly provided by the Schering-Plough Laboratory for Immunological Research, Dardilly, France), more than 95% of the cells were DCs as assessed by CD1a labeling. Cultures of the DCs were performed in 24-well flat-bottomed microtiter plates (Falcon/Becton Dickinson, Le Pont de Claix, France), in a total volume of 1 ml, in RPMI 1640 (Life Technologies) supplemented with 10 mm Hepes (Life Technologies), 2 mm l-glutamine (Life Tech-nologies), 40 g/ml gentamicin (Life Technologies), and 10% FCS (Boehringer Mannheim, Meylan, France).…”

Measles virus hemagglutinin triggers intracellular signaling in CD150-expressing dendritic cells and inhibits immune response

“…Different subsets of DCs, including skin Langerhans cells 4 , peripheral blood DCs 5 , CD34 1 -derived DCs 4 , and monocyte-derived DCs 6 are permissive to MV infection and seem to have subset-specific interferon-inducing systems 7 . Viral infection induces formation of DC syncytia, followed by the loss of the DC's capacity to stimulate naive CD4 1 T cells resulting in inhibition of CD4 1 T-cell proliferation [4][5][6] .…”

“…Different subsets of DCs, including skin Langerhans cells 4 , peripheral blood DCs 5 , CD34 1 -derived DCs 4 , and monocyte-derived DCs 6 are permissive to MV infection and seem to have subset-specific interferon-inducing systems 7 . Viral infection induces formation of DC syncytia, followed by the loss of the DC's capacity to stimulate naive CD4 1 T cells resulting in inhibition of CD4 1 T-cell proliferation [4][5][6] . MV-induced inhibition of T-cell functions was suggested to be mediated through either transmission of infectious virus to T cells, leading to a cell cycle block 8,9 and/or delivery of inhibitory signals via infected DCs [4][5][6] .…”