Format

Send to

Choose Destination
J Clin Virol. 2016 Apr;77:77-84. doi: 10.1016/j.jcv.2016.02.010. Epub 2016 Feb 18.

Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis.

Author information

1
Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany. Electronic address: Almanzar_G@ukw.de.
2
Department of Internal Medicine II, Rheumatology and Immunology, University Hospital Würzburg, Würzburg, Germany.
3
Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany.
4
Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
5
Institute of Pathology, University of Würzburg, Würzburg, Germany.
6
Pediatric Surgery Unit, Department of Surgery, University Hospital Würzburg, Würzburg, Germany.

Abstract

BACKGROUND:

Latent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA).

OBJECTIVES:

Considering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients.

STUDY DESIGN:

Unspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls.

RESULTS:

Despite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA.

DISCUSSION:

CMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients.

KEYWORDS:

Anti-IL-6; Anti-TNFα; CMV; IFNγ; JIA; RA

PMID:
26921739
DOI:
10.1016/j.jcv.2016.02.010
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center