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- Title
Human cytomegalovirus induces a direct inhibitory effect on antigen presentation by monocyte-derived immature dendritic cells.
- Authors
Grigoleit, Ulrich; Riegler, Susanne; Einsele, Hermann; Sampaio, Kerstin Laib; Jahn, Gerhard; Hebart, Holger; Brossart, Peter; Frank, Friderike; Sinzger, Christian
- Abstract
The hypothesis that productive infection of monocyte-derived immature dendritic cells (DCs) by the human cytomegalovirus (HCMV) is associated with decreased immunostimulatory capacity was tested in this study. DCs were infected with 60-80% efficiency by HCMV strain TB40/E. Infected versus uninfected cells were analysed by fluorescence-activated cell sorting and by immunocytochemistry for surface expression of major histo-compatibility complex (MHC) and co-stimulatory molecules as well as cytokine secretion during the 3 d after infection. The immunostimulatory capacity of these cells was measured by mixed leucocyte reaction. Inspite of the fact that HCMV infection of DCs induced an increased release of tumour necrosis factor-α (TNF-α) and a decreased interleukin 10 (IL-10) production, expression of MHC class I and II, as well as CD40 and CD80 molecules, were downregulated on infected DCs. The mixed leucocyte reaction showed significantly reduced immunostimulatory capacity of infected DC cultures. Simultaneous detection of MHC antigens and virus antigens by double immunofluorescence revealed that downregulation occurred only on infected cells, but not on uninfected bystander cells. These findings demonstrate on a single cell level, together with the marked downregulation of MHC and co-stimulatory molecules in the presence of high TNF-α and low IL-10 levels, a direct inhibitory effect of HCMV on antigen presentation by immature DCs independent of soluble mediators.
- Subjects
CYTOMEGALOVIRUS diseases; DENDRITIC cells; ANTIGEN presenting cells
- Publication
British Journal of Haematology, 2002, Vol 119, Issue 1, p189
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1046/j.1365-2141.2002.03798.x