Format

Send to

Choose Destination
J Exp Med. 2014 Sep 22;211(10):2033-45. doi: 10.1084/jem.20140039. Epub 2014 Sep 15.

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

Author information

1
Service of Immunology and Allergy and Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland matthieu.perreau@chuv.ch giuseppe.pantaleo@chuv.ch.
2
Service of Immunology and Allergy and Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
3
INSERM U955, Université Paris Est Créteil, Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Vaccine Research Institute, 94010 Creteil, France.
4
Service of Immunology and Allergy and Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland Swiss Vaccine Research Institute, 1011 Lausanne, Switzerland matthieu.perreau@chuv.ch giuseppe.pantaleo@chuv.ch.

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.

PMID:
25225461
PMCID:
PMC4172212
DOI:
10.1084/jem.20140039
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center