Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo

Abstract

AbstractA disadvantage of umbilical cord blood transplantation (UCBT) is the delay in immune reconstitution, placing patients at increased risk for infections after transplant. Cytomegalovirus (CMV) in particular has been shown to cause significant morbidity in patients undergoing UCBT. Here, we comprehensively evaluate the development of CD4+ and CD8+ T-cell responses to CMV in a cohort of patients that underwent double UCBT. Our findings demonstrate conclusively that a diverse polyclonal CMV-specific T-cell response derived from the UCB graft is primed to viral antigens as early as day 42 after UCBT, but these T cells fail to achieve sufficient numbers in vivo to control CMV reactivations. This is not due to an inherent inability of UCB-derived T cells to proliferate, as these T cells underwent rapid proliferation in vitro. The TCR diversity and antigen specificity of CMV-specific T cells remained remarkably stable in the first year after transplant, suggesting that later control of virus replication results from improved function of T cells primed early after transplant and not from de novo responses derived from later thymic emigrants. Ex vivo expansion and adoptive transfer of CMV-specific T cells isolated from UCBT recipients early after transplant could augment immunity to CMV.