Functional competence of CD8+ T cell responses specific to human cytomegalovirus in common variable immunodeficiency

摘要: This PhD investigated the role of human cytomegalovirus (HCMV) in inflammatory disease associated with common variable immunodeficiency (CVID) by examining functional competence HCMV specific CD8+ T cell responses. The project was based on hypothesis that is a major factor driving expansion cells contribute to pathology. HCMV frequencies were significantly elevated patients compared non-inflammatory or healthy subjects. frequency EBV (GLC) epitope did not differ between patient groups. from displayed distinct cytokine expression profile majority producing IFN-γ only and TNF-α response antigen stimulation. These show evidence exhaustion, low PD-1 expression; rather, they showed high functionality, TCR avidity proliferative potential. but donors expressed levels Ki-67 proliferated stimulation vitro without co-stimulation. Further phenotypic analysis revealed striking correlations expressing granzyme B overall CD27-CD28- cells. Consistent their hypothesized disease, reduced anti-inflammatory marker CD73. support for involvement pathology came collaborative work which viral detected at sites inflammation. The results HCMV-specific are key factors CVID inflammation. They explain previously reported ‘abnormalities’ seen provide an base clinical trials anti-TNF therapy and/or antiviral these patients.