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

摘要

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-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β), and CD107 in addition to interferon-γ (IFN-γ), compared with D⁺/R⁺ recipients. Unlike monofunctional CD8⁺ T cells secreting IFN-γ, 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.