Combined CDS-positive and CD4-positive adenovirus hexon-specific T cells associated with viral clearance after stem cell transplantation as treatment for adenovirus infection

OBJECTIVE To investigate the role of both CD8-positive cytotoxic and CD4-positive helper T cells against the adenovirus hexon protein in protection from adenovirus disease, and to develop a method to allow transfer of these T cells as a treatment option. Human adenovirus can cause morbidity and mortality in immunocompromised patients after allogeneic stem cell transplantation. Reconstitution of adenovirus-specific CD4-positive helper T cells has been reported to be associated with sustained protection from adenovirus disease, but epitope specificity of these responses has not been characterized. DESIGN AND METHODS The presence of T cells specific for adenovirus hexon was analyzed in peripheral blood of paediatric and adult allogeneic stem cell transplantation recipients who showed spontaneous resolution of disseminated adenovirus infection. Isolation of the specific T cells from healthy donors was performed by magnetic separation after antibody labelling. RESULTS Clearance of adenovirus viremia coincided with emergence of a coordinated CD8-positive and CD4-positive T cell response against adenovirus hexon epitopes in patients after allogeneic stem cell transplantation. Specific T cells were efficiently isolated from donor peripheral blood, resulting in adenovirus-specific T cell lines, which were functional and efficiently lysed adenovirus-infected target cells. CONCLUSION This study provides a rationale and strategy for the transfer of donor-derived adenovirus-specific CDS-positive and CD4-positive T cells for the treatment of disseminated adenovirus infection after allogeneic stem cell transplantation.