Perturbations of the CD8+ T-cell repertoire in CVID patients with complications

• Some CVID patients with complications have an increase in peripheral blood CD8+DR+ T cells.
• These CD8+ T-cells have an activated cytotoxic phenotype.
• These CD8+ T-cells show a reduction of their TCR repertoire diversity.
• Viral reactivations such as CMV are suspected leading to accelerated immunosenescence.

A higher chronic expansion of effector cytotoxic CD8+DR+ T-lymphocytes has been reported in common variable immunodeficiency (CVID) patients with complications such as splenomegaly, autoimmune disease and/or granulomatous disease. In order to document the features associated with this T cell activation involving the CD8+ T-compartment, we examined the diversity of the alpha/beta TCR repertoire of the patient's CD8+ T-lymphocytes using the qualitative analysis of the CDR3 lengths (Immunoscope).Ten CIVD patients were enrolled in this study, four without complications (Group 1), six with complications (Group 2). All patients exhibited non-gaussian altered CDR3 length distributions, albeit to different extent within the different Vβ families. CVID patients with activated CD8+ T-cells show a reduction of their TCR repertoire diversity which is more severe in patients with complications. Viral reactivations such as CMV are suspected to be part of the mechanisms underlying immunosenescence.