Analysis of bulk and virus-specific CD8+ T cells reveals advanced differentiation of CD8+ T cells in patients with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency syndrome with alterations in T cell regulation and function in a subgroup of patients. We assessed phenotype and function of bulk and virus-specific CD8+ T cells of a cohort of 34 HLA-A2+ CVID patients by pentamer technology and flow cytometry in relationship to their immunological and clinical phenotypes. Bulk CD8+ T cells displayed a shift toward a more antigen experienced and activated differentiation state. The advanced differentiation pattern was mainly found in a subgroup of CVID patients with lymphadenopathy and granulomatous disease. This effect existed independently of the patients' CMV status even so CMV-associated immunosenescence was more evident in CVID patients than in CMV-positive immunocompetent controls. As the phenotype and function of virus-specific CD8+ T cells were normal in CVID the induction of antiviral immunity by prophylactic immunization appears to be a logical and desirable aim for this group of patients.

► CVID patients show increased terminal differentiation of the CD8+ T cell population.
► CMV infection and lymphadenopathy/granuloma independently aggravate this tendency.
► Virus-specific CD8+ T cells of CVID patients show a regular differentiation pattern.