Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants

  title={Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants},
  author={Loredana Ruggeri and Marusca Capanni and Elena Urbani and Katia Perruccio and Warren D. Shlomchik and Antonella Tosti and Sabrina Posati and Daniela Rogaia and Francesco Frassoni and Franco Aversa and Massimo Fabrizio Martelli and Andr{\'e}a Velardi},
  pages={2097 - 2100}
T cells that accompany allogeneic hematopoietic grafts for treating leukemia enhance engraftment and mediate the graft-versus-leukemia effect. Unfortunately, alloreactive T cells also cause graft-versus-host disease (GVHD). T cell depletion prevents GVHD but increases the risk of graft rejection and leukemic relapse. In human transplants, we show that donor-versus-recipient natural killer (NK)–cell alloreactivity could eliminate leukemia relapse and graft rejection and protect patients against… 

Innate immunity against hematological malignancies.

NK-cell alloreactivity may provide a novel, powerful tool for enhancing the efficacy and safety of allogeneic hematopoietic transplantation.

How important is NK alloreactivity and KIR in allogeneic transplantation?

  • B. ShafferK. Hsu
  • Biology, Medicine
    Best practice & research. Clinical haematology
  • 2016

Hematopoietic stem cell transplantation and cellular therapy

The factors influencing GVHD, ways to exploit rapid advances in knowledge of histocompatibility, chimerism and tolerance for fostering GVL over GV HD, and the use of cellular therapies including donor lymphocyte infusions for disease control are summarized.

Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

The rat as an experimental model of HCT between allogeneic individuals is discussed, the findings on lymphocyte reconstitution in transplanted rats are summarized, and the rat skin explant assay is introduced, a feasible alternative to in vivo transplantation studies.

Alloantigen expression on non-hematopoietic cells reduces graft-versus-leukemia effects in mice.

It is shown, in mouse models of MHC-matched, minor histocompatibility antigen-mismatched bone marrow transplantation, that alloantigen expression on host epithelium drives donor T cells into apoptosis and dysfunction during GVHD, resulting in a loss of GVL activity.

Adoptive Immunotherapy for Acute Myeloid Leukemia: From Allogeneic Hematopoietic Cell Transplantation to CAR T Cells

Novel adoptive immunotherapy strategies have been developed to generate immune response against the leukemic cells, while sparing GVHD.

Hematopoietic stem cell transplantation from full-haplotype mismatched donors.

  • F. Aversa
  • Medicine, Biology
    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis
  • 2002

Immunobiology of allogeneic hematopoietic stem cell transplantation.

Current understanding of some of the issues that affect the success of allogeneic HSCT are reviewed, including host-versus-graft (HVG) reactions, graft-versu-host disease (GVHD), graft-Versus-tumor (GVT) activity, and restoration of functional immunity to prevent transplant-related opportunistic infections.



Transplants across human leukocyte antigen barriers.

T-cell-depleted megadose stem cell transplant from a mismatched family member, who is immediately available, can now be offered as a viable option to candidates with high-risk acute leukemias.

Prevention of graft versus host disease by inactivation of host antigen-presenting cells.

Graft versus host disease, an alloimmune attack on host tissues mounted by donor T cells, is the most important toxicity of allogeneic bone marrow transplantation. The mechanism by which allogeneic T

Megadose of T cell-depleted bone marrow overcomes MHC barriers in sublethally irradiated mice

It is demonstrated in a mouse model that escalation of bone marrow doses by four- to fivefold leads to full donor-type chimerism in sublethally irradiated recipients, and the new source of G-CSF mobilized human haematopoietic stem cells may enable extending the use of mismatched bone marrow transplants to patients with non-malignant diseases for whom supralethal conditioning is not a prerequisite.

Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation.

A GVL effector and engraftment facilitating mechanism, which is independent of T-cell-mediated GVH reactions, may be operational in HLA mismatched hematopoietic cell transplants.

Prevention of allogeneic bone marrow graft rejection by H-2 transgene in donor mice.

Results provide formal evidence that NK cells are part of a system capable of rejecting cells because they lack normal genes of the host type, in contrast to T cells, which recognize cells that contain abnormal or novel sequences of non-host type.

Regulation of hematopoiesis in vitro by alloreactive natural killer cell clones

Data indicate that the alloreactive NK cells are likely the human counterpart of the cells mediating murine hybrid resistance and that these cells might play clinically important roles in rejection or in graft-versus-leukemia reactions after allogeneic bone marrow transplantation.

Successful engraftment of T-cell-depleted haploidentical "three-loci" incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum.

Results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.

Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype.

The main limitations of transplantation of bone marrow from donors who are matched with the recipient for only one HLA haplotype GVHD and graft failure - can be overcome.

Stimulation of mature unprimed CD8+ T cells by semiprofessional antigen- presenting cells in vivo

These cells were nonimmunogenic for most host- reactive CD8+ cells but were capable of stimulating a small subset of high-affinity T cells, and the possible relevance of the data to the prolonged immunogenicity of vascularized allografts in humans is discussed.