4.4 Article

Measles virus interacts with human SLAM receptor on dendritic cells to cause immuno suppression

Journal

VIROLOGY
Volume 323, Issue 2, Pages 292-302

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2004.03.011

Keywords

measles virus; dendritic cells; transgenic mice; immunosuppression; SLAM; lymphocyte proliferation

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Funding

  1. Canadian Institutes of Health Research [37368-1] Funding Source: Medline
  2. NIAID NIH HHS [R01 AI036222, AI36222] Funding Source: Medline

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Measles virus (MV) infects dendritic cells (DCs) resulting in immunosuppression. Human DCs express two MV receptors: CD46 and human signaling lymphocyte activation molecule (hSLAM); thus, the role played by either alone is unclear. Because wild-type (wt) MV uses hSLAM receptor preferentially, we dissected the molecular basis of MV-DC interaction and resultant immunosuppression through the hSLAM receptor by creating transgenic (tg) mice expressing hSLAM on DCs. After infection with wt MV, marine splenic DCs expressing hSLAM receptor had less B7-1, B7-2, CD40, MHC class I, and MHC class II molecules on their surfaces and displayed an increased rate of apoptosis when compared to uninfected DCs. Further, MV-infected DCs failed to stimulate allogeneic T cells and inhibited mitogen-dependent T-cell proliferation. Individual expression of human SLAM, interferon alpha/beta receptor, tumor necrosis factor-a, and lymphotoxin-a or beta from T cells was not required for MV-infected DCs to inhibit the proliferation of T cells. (C) 2004 Elsevier Inc. All rights reserved.

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