PMID- 11929782
OWN - NLM
STAT- MEDLINE
DCOM- 20020617
LR  - 20211203
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 99
IP  - 8
DP  - 2002 Apr 15
TI  - Human cytomegalovirus inhibits maturation and impairs function of 
      monocyte-derived dendritic cells.
PG  - 2913-21
AB  - Dendritic cells (DCs) play a pivotal role in the generation of virus-specific 
      cytotoxic T-cell responses, but some viruses can render DCs inefficient in 
      stimulating T cells. We studied whether infection of DCs with human 
      cytomegalovirus (HCMV) results in a suppression of DC function which may assist 
      HCMV in establishing persistence. The effect of HCMV infection on the phenotype 
      and function of monocyte-derived DCs and on their ability to mature following 
      infection with an endothelial cell-adapted clinical HCMV isolate were studied. 
      HCMV infection induced no maturation of DCs; instead, it efficiently 
      down-regulated the expression of surface major histocompatibility complex (MHC) 
      class I, CD40, and CD80 molecules. Slight down-regulation of MHC class II and 
      CD86 molecules was also observed. Lipopolysaccharide (LPS)-induced maturation of 
      infected DCs was strongly inhibited, as indicated by lower levels of surface 
      expression of MHC class I, class II, costimulatory, and CD83 molecules. The 
      down-regulation or inhibition of these surface markers occurred only in HCMV 
      antigen-positive DCs. DCs produced no interleukin 12 (IL-12) and only low levels 
      of tumor necrosis factor alpha (TNF-alpha) upon HCMV infection. Furthermore, 
      cytokine production upon stimulation with LPS or CD40L was significantly 
      impaired. Inhibition of cytokine production did not depend on viral gene 
      expression as UV-irradiated HCMV resulted in the same effect. Proliferation and 
      cytotoxicity of T cells specific to a recall antigen presented by DCs were also 
      reduced when DCs were HCMV infected. This study shows that HCMV inhibits DC 
      function, revealing a powerful viral strategy to delay or prevent the generation 
      of virus-specific cytotoxic T cells.
FAU - Moutaftsi, Magdalena
AU  - Moutaftsi M
AD  - Section of Infection and Immunity, University of Wales College of Medicine, 
      Cardiff, United Kingdom.
FAU - Mehl, Anja M
AU  - Mehl AM
FAU - Borysiewicz, Leszek K
AU  - Borysiewicz LK
FAU - Tabi, Zsuzsanna
AU  - Tabi Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Cytokines)
RN  - 0 (HLA Antigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Cell Differentiation
MH  - Cytokines/metabolism
MH  - Cytomegalovirus/*physiology
MH  - Cytomegalovirus Infections/immunology/pathology
MH  - Dendritic Cells/cytology/*immunology/*virology
MH  - Down-Regulation
MH  - HLA Antigens/metabolism
MH  - Humans
MH  - Immunosuppression Therapy
MH  - Interleukin-12/metabolism
MH  - Lymphocyte Activation/immunology
MH  - Monocytes/cytology
MH  - T-Lymphocytes, Cytotoxic/immunology/virology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2002/04/04 10:00
MHDA- 2002/06/18 10:01
CRDT- 2002/04/04 10:00
PHST- 2002/04/04 10:00 [pubmed]
PHST- 2002/06/18 10:01 [medline]
PHST- 2002/04/04 10:00 [entrez]
AID - S0006-4971(20)37979-9 [pii]
AID - 10.1182/blood.v99.8.2913 [doi]
PST - ppublish
SO  - Blood. 2002 Apr 15;99(8):2913-21. doi: 10.1182/blood.v99.8.2913.