Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients

Reconstitution of cytomegalovirus (CMV) specific CD8(+) T cells is essential to the control of CMV infection in CMV-positive recipients (R+) after allogeneic hematopoietic stem cell transplantation (HCT). Six-color flow cytometry was used to assess the functional profile of CMV-specific CD8(+) T cells in 62 of 178 R+ HCT recipients followed virologically for CMV reactivation. R+ recipients receiving grafts from CMV- negative donors (D-; D-/R+) reconstituted fewer multifunctional CD8(+) T cells expressing tumor necrosis factor-alpha( TNF-alpha), macrophage inflammatory protein-1 beta (MIP-1 beta), and CD107 in addition to interferon-gamma (IFN-gamma), compared with D-/R+ recipients. Unlike monofunctional CD8(+) T cells secreting IFN-gamma, which were abundantly generated during CMV reactivation in D-/R+ recipients, the relative lack of multifunctional CD8(+) T cells persisted until at least 1 year post-HCT. D-/R+ recipients were more likely to require recurrent and prolonged use of antivirals. These findings were robust to statistical adjustment for pretransplant factors, as well as for posttransplant factors including graft-versus-host disease (GVHD) and its treatment by steroids. These analyses suggest that D-/R+ transplants, on average, generate higher levels of multifunctional CMV-specific T cells and require less antiviral therapy compared with D-/R+ HCT recipients. These results highlight the benefit of D+ donors in improving outcomes of R+ HCT recipients by reducing the duration and recurrent need of antiviral treatment, aided by increased levels of multifunctional CMV-specific T cells. ( Blood. 2009; 113: 6465-6476)