T-cell recovery in adults and children following umbilical cord blood transplantation

Abstract

T-cell reconstitution following allogeneic stem cell transplantation may involve thymic education of donor-derived precursors or peripheral expansion of mature T cells transferred in the graft. T cell-receptor excision circles (sjTRECs) are generated within the thymus and identify new thymic emigrants and those that have not divided. We measured quantitative and qualitative immunologic reconstitution and sjTREC levels in adult and pediatric recipients of umbilical cord blood transplants (UCBTs). sjTRECs were detected at normal levels in all children, starting 12 months after transplantation. sjTRECs were not detected until 18 months after transplantation in adults, and then only at a 3-fold lower level than expected for age. We used complementarity-determining region 3 (CDR3) spectratyping to measure changes in T cell-receptor diversity occurring with restoration of thymic function. T-cell repertoires were skewed in adults and children at 12 to 18 months after transplantation but recovered to near-normal diversity at 2 to 3 years post-UCBT. T-cell repertoires appeared more diverse earlier in children (at 1 to 2 years post-UCBT) than in adults (at 3 to 4 years post-UCBT). We conclude that early T-cell recovery after UCBT occurs primarily through peripheral expansion of adoptively transferred donor T cells and results in skewing of the T-cell repertoire. The reappearance of sjTREC-containing cells after UCBT is associated with increasing numbers of phenotypicaly naive T cells, improved mitogen and recall antigen responses, and diversification of the T-cell repertoire. The delay in central T-cell recovery in adults relative to children may be due to differences in thymic function resulting from age-related atrophy, graft-versus-host disease, or the pharmacologic effects of prophylaxis and treatment of graft-versus-host disease.

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

“…Several reports outlining the kinetics of immune recovery after UCB transplantation in adults and children point to slow T-cell recovery [60], [62][63][64][65][66] compared with published reports after conventional graft allogeneic transplantation [66][67][68][69][70][71]. Recent studies have evaluated the immune function of adult UCB patients during the first two years post-transplant.…”

“…The mechanism and significance of this B-cell 'rebound' phenomenon observed post-transplant in adult UCB recipients is unclear. Work from the Duke University program reported that T-cell recovery was comparable in adults and children following UCB transplant [64]. This event was associated with delayed emergence of thymic recent emigrants cells (TREC) in adults (18 months) vs. children (12 months) as well as lower levels than expected for age.…”

Immune restoration following hematopoietic stem cell transplantation: an evolving target

“…Children have more enhanced recovery of naı¨ve T cells (CD4 þ CD45RA þ ), greater thymic rebound, more diverse TCR, and higher TREC levels than their adult counterparts. [33][34][35] Faster CD4 þ recovery has been correlated with better protection against infection in pediatric vs adult T-cell-depleted BMT 36 and overall patient outcome in peripheral blood stem cell transplantation (PBSCT) from HLA-identical siblings or alternative family donors. 37 Second, pediatric patients seem to have less incidence of GVHD when compared to their adult counterparts.…”

Disseminated tuberculosis following reduced-intensity cord blood transplantation for adult patients with hematological diseases

“…Functional immune recovery begins 3 months after conventional UCBT in adult patients, and T-cell reconstitution begins by 18 months. 29 Table 3 Phenotypic analysis of peripheral lymphocytes at the onset of tuberculosis Tuberculosis after RI-UCBTChronic GVHD, immunosuppressive therapy, TBI and Tcell depletion have been shown to be risk factors for tuberculosis following conventional allo-HSCT. 16,17,30 We used a TBI-containing preparative regimen, and two patients developed either GVHD or pre-engraftment immune reaction, requiring corticosteroid.…”