Natural Killer Cell Alloreactivity in Haploidentical Hematopoietic Stem Cell Transplantation

Abstract

Natural killer (NK) cells are primed to kill by several activating receptors. NK cell killing of autologous cells is prevented because NK cells coexpress inhibitory receptors (killer cell immunoglobulin-like receptors [KIR]) that recognize groups of (self) major histocompatibility complex class I alleles. Because KIRs are clonally distributed, the NK cell population in any individual are constituted of a repertoire with a variety of class I specificities. NK cells in the repertoire mediate alloreactions when the allogeneic targets do not express the class I alleles that block them. After haploidentical hematopoietic transplantation, NK cell-mediated donor-versus-recipient alloresponses reduce the risk of relapse in acute myeloid leukemia patients while improving engraftment and protecting against graft-versus-host disease. High-resolution molecular HLA typing of recipient and donor, positive identification of donor KIR genes, and, in some cases, functional assessment of donor NK clones identify haploidentical donors who are able to mount donor-versus-recipient NK alloreactions.

Analysis of the activating receptors and cytolytic function of human natural killer cells undergoing in vivo differentiation after allogeneic bone marrow transplantation

“…In allogeneic BMT, they may also mediate graft-versus-leukemia [16,17]. Indeed, it has been shown that NK cells in patients undergoing haploidentical BMT may play a pivotal role in the depletion of residual leukemic cells, thus preventing leukemic relapses [18,19]. Moreover, in BMT patients, NK cells may play a role in the control of EBV reactivation, a complication of allogeneic BMT that can cause serious and often fatal lymphoproliferative disease after transplant [20][21][22][23].…”

“…Lymphocytes recovered in patients undergoing allogeneic BMT were analyzed at different time intervals, starting from engraftment (occurring at day [12][13][14][15][16][17][18][19][20].…”

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

“…Minor histocompatibility disparity in unrelated allogeneic transplantation may contribute to graft rejection and to graftversus-leukemia effects [38][39][40][41]. HLA class I mismatching including HLA-C and NK epitope mismatching are associated with higher rates of graft rejection and severe acute GVHD after unrelated donor transplantation [42,43]. Allele matching for adult unrelated blood and marrow grafting has improved rates of engraftment and GVHD.…”

The Killer Immunoglobulin-Like Receptor (KIR) Group A Haplotype is Associated With Bronchiolitis Obliterans Syndrome After Lung Transplantation

“…HLA-C and HLA-B were segregated into the epitopes groups HLA-C group 1 (HLA-C Asn 80: HLACw1,3,7,8,13,14 alleles), HLA-C group 2 (HLA-Clys80: HLA-Cw2,4,5,6,12,15,17,18 alleles), and HLA-Bw4. 20 DNA from patients was typed for 6 activating KIR genes (2DS1, 2DS2, 2DS3, 2DS4, 2DS5, and 3DS1) and for 8 inhibitory KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DL2, and 3DL3) by LUMINEX SSO (One Lambda Inc, Canoga Park, CA). A missing KIR ligand was defined as the presence of patients' KIR genes in the absence of their corresponding HLA on the transplanted lungs (ligand).…”