Infection of mature monocyte-derived dendritic cells with human cytomegalovirus inhibits stimulation of T-cell proliferation via the release of soluble CD83 Journal Article
| Authors: | Senechal, B.; Boruchov, A. M.; Reagan, J. L.; Hart, D. N. J.; Young, J. W. |
| Article Title: | Infection of mature monocyte-derived dendritic cells with human cytomegalovirus inhibits stimulation of T-cell proliferation via the release of soluble CD83 |
| Abstract: | We have studied the mechanisms by which human cytomegalovirus (HCMV) infection of monocyte-derived dendritic cells (moDCs) contribute to immune suppression. Unlike infection of immature moDCs, infection of mature moDCs is not lytic and results in minimally decreased surface major histocompatibility complex (MHC) and costimulatory molecule expression. The presence of a small percentage of CMV-infected mature moDCs, or the transfer of supernatant from infected moDCs depleted of infectious virions, is nevertheless sufficient to cause marked inhibition of immunostimulation by normal uninfected moDCs. Neither viral nor human interleukin 10 (IL-10) nor transforming growth factor-β-1 (TGF-β-1) could account for this inhibition. In contrast, we show that infected mature moDCs lose surface CD83 while maintaining intracellular protein expression. Soluble CD83 accumulates in the supernatants of CMV-infected mature moDCs, and CD83 immunodepletion removes the inhibitory effect of these supernatants on normal DC immunostimulation. We have thus discovered a new mechanism by which HCMV infection may establish a nonlytic reservoir in mature moDCs that inhibits DC-mediated T-cell responses. © 2004 by The American Society of Hematology. |
| Keywords: | controlled study; protein expression; human cell; cell proliferation; t lymphocyte; t-lymphocytes; cell survival; cell division; dendritic cell; interleukin 10; down-regulation; dendritic cells; lymphocyte culture test, mixed; membrane glycoproteins; transforming growth factor beta1; immunostimulation; antigens, cd; virus replication; monocytes; immunosuppressive treatment; major histocompatibility complex; immediate-early proteins; cytomegalovirus infection; cytomegalovirus; cd83 antigen; immunoglobulins; viral proteins; solubility; human cytomegalovirus; cytomegalovirus infections; humans; human; priority journal; article |
| Journal Title: | Blood |
| Volume: | 103 |
| Issue: | 11 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2004-06-01 |
| Start Page: | 4207 |
| End Page: | 4215 |
| Language: | English |
| DOI: | 10.1182/blood-2003-12-4350 |
| PROVIDER: | scopus |
| PUBMED: | 14962896 |
| DOI/URL: | |
| Notes: | Blood -- Cited By (since 1996):90 -- Export Date: 16 June 2014 -- CODEN: BLOOA -- Source: Scopus |
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