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

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 IFN gamma-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 IFN-gamma responses in arthritis patients. Study design: Unspecific and CMVpp65-specific IFN gamma 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 IFN-gamma production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFN gamma production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNF alpha or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA. Discussion: CMVpp65-specific IFN-gamma production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNF alpha. or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFN gamma-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 IFN gamma-mediated inflammatory potential of CD8+ T-cells in arthritis patients. (C) 2016 Elsevier B.V. All rights reserved.