Complementary and contrasting roles of NK cells and T cells in pediatric umbilical cord blood transplantation

Abstract

UCBT has been used for almost 25 years to treat a variety of malignant and nonmalignant childhood diseases. The biological properties of NK cells and T cells and their implication in engraftment, immune reconstitution, OIs, leukemic relapse, and GvHD have been explored in the context of UCBT. These studies have established that lymphocytes have a major impact on the outcome of UCBT and that NK cells and T cells play complementary and contrasting roles in immune reconstitution and the GvL effect. Therefore, novel strategies to improve the outcome of UCBT recipients, including immunotherapeutic regimens, should be based on key immunologic features of UCB T lymphocytes and NK cells.

Reconstitution of Protective Immune Responses against Cytomegalovirus and Varicella Zoster Virus Does Not Require Disease Development in Pediatric Recipients of Umbilical Cord Blood Transplantation

“…Reflecting T cell reconstitution, the number of subjects in whom CMV-and VZV-specific responses were detectable increased between 6 and 36 mo posttransplantation, but the respective kinetics of reconstitution of responses against these two pathogens were not significantly different. This is despite the reported differences in timing of CMVassociated (early) versus VZV-associated (late) infectious complications relative to the time of transplant, perhaps reflecting the differential efficacy of cell-mediated immunity in controlling these two particular pathogens (8,9,(12)(13)(14)31).…”

“…That likely explains the specific pattern of clinical outcomes associated with UCBT in comparison with BMT. Major advantages of UCBT include a low incidence of graft-versus-host disease (GvHD) (4) and an efficient graft-versusleukemia effect (5) graftment, late reconstitution of the CD8 + T cell subset, and a higher incidence of opportunistic infections in the first 3-6 mo posttransplantation that results in higher morbidity and mortality relative to BMT during this period (6)(7)(8). In particular, CMV and varicella zoster virus (VZV) are important causes of opportunistic infections, and infections with these pathogens are observed more frequently in UCBT recipients than in BMT recipients (9,10).…”

Cellular engineering and therapy in combination with cord blood allografting in pediatric recipients

“…21 Inhibitory members of the killer cell immunoglobulin-like (KIR) and NKG2-family receptors recognize self HLA class I antigens, and activating receptors recognize stress ligands, viral proteins and antibodies on target cells. NK cell reconstitution after UCBT precedes T-or B-cell reconstitution by about 2 months (around day 30 vs day 100), 22 and is a critical in providing compensatory immune function in the face of T-cell reconstitution, which is further delayed in UCBT compared with marrow or peripheral blood HSCT. 23 In the early post-CBT period, NK cells preferentially express the inhibitory receptor NKG2A with reduced KIR expression, indicating that mature NK cells are present in low proportions.…”

The impact of donor and recipient KIR genes and KIR ligands on the occurrence of acute graft-versus-host disease and graft survival after HLA-identical sibling hematopoietic stem cell transplantation

“…There is evidence that allogeneic HLA-matched transplantation for patients with lymphoblastic and myeloblastic leukemia is more effective than autogeneic transplantation, because allo-HSCT may induce the graftversus-leukemia (GVL) effect (3,4). The potential benefit of the GVL effect relies on the elimination of residual malignant cells through immunological antitumor effects, induced by alloreactive T and natural killer (NK) cells, which leads to a lower relapse rate in allo-HSCT patients with hematologic malignancies (3,5,6). Despite all the advantages of allo-HSCT, there are still some complications that limit the success of this important procedure, including the development of graft-versushost disease (GVHD) (7).…”

“…In allo-HSCT, NK cells have been recognized as a novel factor in the effector system that can overcome natural alloreactive T-cell barriers (6). Alloreactive donor NK cells facilitate engraftment by ablating different cells including residual leukemic cells, APCs, and T cells responsible for triggering GVHD (4,5,(13)(14)(15).…”