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Review
. 2017 Apr 25:8:465.
doi: 10.3389/fimmu.2017.00465. eCollection 2017.

Natural Killer Cells in Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation

Federico Simonetta  1   2 , Maite Alvarez  1 , Robert S Negrin  1
Affiliations
Review

Natural Killer Cells in Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation

Federico Simonetta et al. Front Immunol. .

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is a well-established therapeutic modality effective for a variety of hematological malignancies but, unfortunately, is associated with significant morbidity and mortality related to cancer relapse as well as to transplant-related complications including graft-versus-host-disease (GvHD). Natural killer (NK) cells are the first donor-derived lymphocyte subset to recover after HCT, and their crucial role in protection against cancer relapse and infections is well established. Conversely, the role played by NK cells in GvHD is still controversial. Early studies suggested a participation of NK cells in GvHD induction or exacerbation. Subsequently, experimental evidence obtained in mice as well observational studies performed in humans led to a model in which NK cells play a regulatory role in GvHD by repressing alloreactive T cell responses. This widely accepted model has been recently challenged by clinical evidence indicating that NK cells can in some cases promote GvHD. In this review, we summarize available knowledge about the role of NK cells in GVHD pathogenesis. We review studies uncovering cellular mechanisms through which NK cells interact with other immune cell subsets during GvHD leading to a model in which NK cells naturally suppress GvHD through their cytotoxic ability to inhibit T cell activation unless exogenous hyperactivation lead them to produce proinflammatory cytokines that can conversely sustain T cell-mediated GvHD induction.

Keywords: HSCT; bone marrow transplantation; graft-versus-host-disease; natural killer cells; tolerance.

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Figures

Figure 1
Figure 1
NK cells contribution to graft-versus-host-disease (GvHD) protection or induction. Immunological interactions leading to GvHD protective (left panel) or promoting (right panel) effect of NK cells. Donor immune cells are depicted in blue while host target cells are depicted in orange. NK, natural killer; T, T lymphocyte; APC, antigen-presenting cell; IFN-γ, interferon-γ; TNF-α, tumor necrosis factor-α.
See this image and copyright information in PMC

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