The T cell response to persistent herpes virus infections in common variable immunodeficiency

Abstract

SummaryWe show that at least half of patients with common variable immunodeficiency (CVID) have circulating CD8+ T cells specific for epitopes derived from cytomegalovirus (CMV) and/or the Epstein-Barr virus (EBV). Compared to healthy age-matched subjects, more CD8 + T cells in CVID patients were committed to CMV. Despite previous reports of defects in antigen presentation and cellular immunity in CVID, specific CD4+ and CD8 + T cells produced interferon (IFN)-g after stimulation with CMV peptides, and peripheral blood mononuclear cells secreted perforin in response to these antigens. In CVID patients we found an association between a high percentage of circulating CD8 + CD57 + T cells containing perforin, CMV infection and a low CD4/CD8 ratio, suggesting that CMV may have a major role in the T cell abnormalities described previously in this disease. We also show preliminary evidence that CMV contributes to the previously unexplained severe enteropathy that occurs in about 5% of patients.

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

“…Treatment of CVID patients with anti-TNF-alpha therapy (infliximab) reduces inflammatory disease (67), and the inhibition of CMV replication with antiviral drugs (ganciclovir) has a comparable effect (64). These findings provide a rationale for antiviral and anti-TNF-alpha therapy in CVID patients with inflammatory disease.…”

T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections

“…The possibility of an infectious agent driving the clinical manifestations of lymphoproliferation observed in the PL subset of CVID patients has been suggested, but not established -a hypothesis supported by these T cell phenotypes. It has been suggested that cytomegalovirus (CMV) may play a role in the T cell abnormalities seen in CVID, as patients in one study had a 13-fold increased proportion of CMV-specific, functional T cells compared to aged-matched controls [29]. CMV-specific CD8 T cells have the phenotype of CD45RA…”

Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency

“…CMV status was determined by means of serology for healthy subjects or, for patients with CVID in whom results of serologic assays are uninformative, by means of measurement of virusspecific CD4 1 T-cell responses, as previously described. 10,11 Three patients (1 CMV-positive and 2 CMV-negative patients) were excluded from analysis because of the presence of mutations in the TNF receptor family member transmembrane activator and cyclophilin ligand interactor gene (TNFRSF13B). A subset of the CMV-positive patients (25 patients with CVID and 14 control subjects) were included in further studies of T-cell function.…”