Autologous human cytomegalovirus-specific cytotoxic T cells as rescue therapy for ulcerative enteritis in primary immunodeficiency

PURPOSE:Patients affected by primary immunodeficiency usually undergo a wide range of infections, including reactivation of latent ones. Here we report two cases suffering from late-onset combined immunodeficiency in which ulcerative enteritis due to human Cytomegalovirus caused a life-threatening malabsorption syndrome. METHODS: The assessment of the viral load was carried out on both blood and mucosal samples by quantitative real-time polymerase chain reaction assay. The generation of autologous virus-specific cytotoxic T cell lines was performed according to Good Manufacturing Practice protocol after peripheral blood mononuclear cells were collected through a single leukapheresis. RESULTS: In both patients, the viral load resulted negligible in peripheral blood, but very high in mucosal specimens (range 1.064 - 1.031.692 copies/10(5) cells). After two rounds of antiviral therapy proved unsuccessful, the generation of virus-specific cytotoxic T cell lines was carried out despite severe lymphopenia, and their infusion resulted safe and durably effective in healing intestinal ulcerations and resetting the viral load. CONCLUSIONS: Virus-specific cellular therapy was useful in reconstituting specific immunity and treating severe human Cytomegalovirus-related enteritis in patients with primary immunodeficiency.