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Transplantation and innate immunity: the lesson of natural killer cells.

Bertaina A, Locatelli F, Moretta L - Ital J Pediatr (2009)

Bottom Line: Natural killer cells have been demonstrated to play a major role in mediating an anti-leukemia effect in patients given a T-cell depleted allogeneic hematopoietic stem cell transplantation from an HLA-haploidentical family donor.A recent study on high-risk pediatric acute lymphoblastic leukemia refractory to chemotherapy further highlighted the importance of donors with alloreactive natural killer cells in haploidentical hematopoietic stem cell transplantation, as it demonstrated that these cells can emerge starting from the fourth-fifth month after the allograft and persist for many months.This study represents a major breakthrough in the cure of otherwise fatal leukemias, providing information on the best criteria for choosing the optimal donor.

View Article: PubMed Central - HTML - PubMed

Affiliation: Paediatric Haematology/Oncology, University of Pavia, Foundation IRCCS Policlinico San Matteo, Pavia, Italy.

ABSTRACT
Natural killer cells have been demonstrated to play a major role in mediating an anti-leukemia effect in patients given a T-cell depleted allogeneic hematopoietic stem cell transplantation from an HLA-haploidentical family donor. In particular, donor-derived natural killer cells, which are alloreactive (i.e. KIR/HLA mismatched) towards recipient cells, significantly contribute to the eradication of leukemia blasts escaping the preparative regimen to transplantation. A recent study on high-risk pediatric acute lymphoblastic leukemia refractory to chemotherapy further highlighted the importance of donors with alloreactive natural killer cells in haploidentical hematopoietic stem cell transplantation, as it demonstrated that these cells can emerge starting from the fourth-fifth month after the allograft and persist for many months. This study represents a major breakthrough in the cure of otherwise fatal leukemias, providing information on the best criteria for choosing the optimal donor.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the main interactions occurring between normal natural killer (NK) cells (expressing both HLA class I-specific inhibitory receptors and activating receptors) and potential target cells. Normal tissues deliver inhibitory signals, which block NK cells (a). Normal stressed tissues deliver simultaneously both activatory and inhibitory signals, this also resulting in block of the lytic capacity of NK cells (b). The lack of inhibitory signals, by contrast, permits NK cells to kill their targets, activatory signals playing a facilitating role (c). Modified from Moretta et al. Immunology Today 2004.
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Figure 1: Schematic representation of the main interactions occurring between normal natural killer (NK) cells (expressing both HLA class I-specific inhibitory receptors and activating receptors) and potential target cells. Normal tissues deliver inhibitory signals, which block NK cells (a). Normal stressed tissues deliver simultaneously both activatory and inhibitory signals, this also resulting in block of the lytic capacity of NK cells (b). The lack of inhibitory signals, by contrast, permits NK cells to kill their targets, activatory signals playing a facilitating role (c). Modified from Moretta et al. Immunology Today 2004.

Mentions: NK cells are key members of the natural immune system, which each single individual possesses, and are of fundamental importance to limit or eradicate pathogens during the early phases of a primary infection, i.e. before T and B cells can mount efficient responses [5,10]. Indeed, NK cells and phagocytes do not require clonal expansion and can enter and defend a tissue almost as soon as it becomes infected. NK cells, derived from the haematopoietic progenitors through a common lymphoid progenitor [10], play a pivotal role in the defense against viral infections and transformed cells. The molecular mechanisms that allow NK cells to spare normal cells and kill tumor or virus-infected cells are represented by the interplay between an array of surface receptors with either activating or inhibitory function [5,10]. Indeed, NK-cell function results from the net balance between activatory and inhibitory signals (see also Figure 1). The role played by inhibitory signals represents a peculiarity of NK cells in comparison to the function of both T and B lymphocytes which is regulated only by activatory signals, and the signals delivered by inhibitory receptors present on the surface of NK lymphocytes are even more important than the activatory signals [5,10,11]. NK receptors are known as Killer Immunoglobulin-like receptors (KIR), and the inhibitory ones specifically interact with determinants that are shared by different HLA-class I molecules (referred to as KIR ligands). In a self environment, to ensure self tolerance, each individual NK cell expresses at least one inhibitory receptor specific for autologous HLA-class I and an NK-mediated attack towards autologous cells occurs only when these do not express at all or express low amounts of HLA class-I molecules.


Transplantation and innate immunity: the lesson of natural killer cells.

Bertaina A, Locatelli F, Moretta L - Ital J Pediatr (2009)

Schematic representation of the main interactions occurring between normal natural killer (NK) cells (expressing both HLA class I-specific inhibitory receptors and activating receptors) and potential target cells. Normal tissues deliver inhibitory signals, which block NK cells (a). Normal stressed tissues deliver simultaneously both activatory and inhibitory signals, this also resulting in block of the lytic capacity of NK cells (b). The lack of inhibitory signals, by contrast, permits NK cells to kill their targets, activatory signals playing a facilitating role (c). Modified from Moretta et al. Immunology Today 2004.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806872&req=5

Figure 1: Schematic representation of the main interactions occurring between normal natural killer (NK) cells (expressing both HLA class I-specific inhibitory receptors and activating receptors) and potential target cells. Normal tissues deliver inhibitory signals, which block NK cells (a). Normal stressed tissues deliver simultaneously both activatory and inhibitory signals, this also resulting in block of the lytic capacity of NK cells (b). The lack of inhibitory signals, by contrast, permits NK cells to kill their targets, activatory signals playing a facilitating role (c). Modified from Moretta et al. Immunology Today 2004.
Mentions: NK cells are key members of the natural immune system, which each single individual possesses, and are of fundamental importance to limit or eradicate pathogens during the early phases of a primary infection, i.e. before T and B cells can mount efficient responses [5,10]. Indeed, NK cells and phagocytes do not require clonal expansion and can enter and defend a tissue almost as soon as it becomes infected. NK cells, derived from the haematopoietic progenitors through a common lymphoid progenitor [10], play a pivotal role in the defense against viral infections and transformed cells. The molecular mechanisms that allow NK cells to spare normal cells and kill tumor or virus-infected cells are represented by the interplay between an array of surface receptors with either activating or inhibitory function [5,10]. Indeed, NK-cell function results from the net balance between activatory and inhibitory signals (see also Figure 1). The role played by inhibitory signals represents a peculiarity of NK cells in comparison to the function of both T and B lymphocytes which is regulated only by activatory signals, and the signals delivered by inhibitory receptors present on the surface of NK lymphocytes are even more important than the activatory signals [5,10,11]. NK receptors are known as Killer Immunoglobulin-like receptors (KIR), and the inhibitory ones specifically interact with determinants that are shared by different HLA-class I molecules (referred to as KIR ligands). In a self environment, to ensure self tolerance, each individual NK cell expresses at least one inhibitory receptor specific for autologous HLA-class I and an NK-mediated attack towards autologous cells occurs only when these do not express at all or express low amounts of HLA class-I molecules.

Bottom Line: Natural killer cells have been demonstrated to play a major role in mediating an anti-leukemia effect in patients given a T-cell depleted allogeneic hematopoietic stem cell transplantation from an HLA-haploidentical family donor.A recent study on high-risk pediatric acute lymphoblastic leukemia refractory to chemotherapy further highlighted the importance of donors with alloreactive natural killer cells in haploidentical hematopoietic stem cell transplantation, as it demonstrated that these cells can emerge starting from the fourth-fifth month after the allograft and persist for many months.This study represents a major breakthrough in the cure of otherwise fatal leukemias, providing information on the best criteria for choosing the optimal donor.

View Article: PubMed Central - HTML - PubMed

Affiliation: Paediatric Haematology/Oncology, University of Pavia, Foundation IRCCS Policlinico San Matteo, Pavia, Italy.

ABSTRACT
Natural killer cells have been demonstrated to play a major role in mediating an anti-leukemia effect in patients given a T-cell depleted allogeneic hematopoietic stem cell transplantation from an HLA-haploidentical family donor. In particular, donor-derived natural killer cells, which are alloreactive (i.e. KIR/HLA mismatched) towards recipient cells, significantly contribute to the eradication of leukemia blasts escaping the preparative regimen to transplantation. A recent study on high-risk pediatric acute lymphoblastic leukemia refractory to chemotherapy further highlighted the importance of donors with alloreactive natural killer cells in haploidentical hematopoietic stem cell transplantation, as it demonstrated that these cells can emerge starting from the fourth-fifth month after the allograft and persist for many months. This study represents a major breakthrough in the cure of otherwise fatal leukemias, providing information on the best criteria for choosing the optimal donor.

No MeSH data available.


Related in: MedlinePlus