Single-Cell Analysis of Adaptive NK and CMV-Specific T Cell Dynamics after Allogeneic HSCT

Area of Science:

• Immunology
• Transplantation Biology
• Virology

Background:

• Cytomegalovirus (CMV) reactivation is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT), affecting immune reconstitution, morbidity, and mortality.
• Understanding the dynamics of immune recovery, particularly in the context of asymptomatic CMV viremia, is crucial for improving patient outcomes.

Purpose of the Study:

• To investigate the impact of asymptomatic CMV reactivation on immune reconstitution following HSCT.
• To characterize the development of T-cell and NK-cell responses in relation to donor cytomegalovirus serostatus.

Main Methods:

• Longitudinal profiling of blood samples from donor-recipient pairs using single-cell RNA and TCR sequencing.
• Analysis of T cells specific to the CMV pp65 epitope and adaptive NK cell maturation.
• Assessment of T-cell chimerism and repertoire expansion.

Main Results:

• Early expansion of monocytes, T cells, and NK cells post-HSCT, with persistent patient CD4+ T cell chimerism.
• Slower maturation of CMV-specific T cells and adaptive NK cells in recipients of grafts from CMV-seronegative donors.
• Rapid adaptive NK cell maturation in CMV-seropositive donor recipients, with higher cytotoxicity observed in CMV-seronegative donor recipients.
• Dominant CD8+ T cell expansions targeting the CMV pp65 epitope, exhibiting terminal maturation.

Conclusions:

• Donor CMV serostatus significantly influences the pace and profile of immune reconstitution after HSCT in the presence of CMV reactivation.
• Findings provide insights into predicting immune recovery timing and inform strategies for managing post-transplant complications related to CMV.
• This study offers a comprehensive single-cell transcriptomic view of adaptive immune recovery post-HSCT with a focus on CMV.