Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders.

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Version: Final published version
Serval ID
serval:BIB_4C2E49D53264
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders.
Journal
Journal of Experimental Medicine
Author(s)
Perreau M., Vigano S., Bellanger F., Pellaton C., Buss G., Comte D., Roger T., Lacabaratz C., Bart P.A., Levy Y., Pantaleo G.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
211
Number
10
Pages
2033-2045
Language
english
Notes
Publication types: Journal Article Publication Status: ppublishThis article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Abstract
In the present study, we have investigated the functional profile of CD4 T cells from patients with common variable immunodeficiency (CVID), including production of cytokines and proliferation in response to bacteria and virus-derived antigens. We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. High levels of endotoxins were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be caused by bacterial translocation. Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. In conclusion, the present study demonstrates that the CD4 T cell exhaustion and functional impairment observed in CVID patients is associated with bacterial translocation and that IVIG treatment resolves bacterial translocation and restores CD4 T cell functions.
Pubmed
Web of science
Open Access
Yes
Create date
24/10/2014 12:40
Last modification date
20/08/2019 14:00
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