Abstract
Natural killer (NK) cells are key members of the innate immune system. In a self-environment, they sense and kill target cells lacking major histocompatibility complex class I molecules and release various cytokines on activation. The discovery of human leukocyte antigen (HLA) class I specific inhibitory receptors (including the allotype-specific killer immunoglobulin-like receptors), and of various activating receptors and their ligands, provided the basis for understanding the molecular mechanism of NK-cell activation and function, mainly resulting from the balance between activating and inhibitory signals. In an allogeneic setting, such as T cell-depleted haploidentical hematopoietic stem cell transplantation, NK cells may express inhibitory killer immunoglobulin-like receptors that are not engaged by any of the HLA class I alleles present on allogeneic cells. Such "alloreactive" NK cells greatly contribute both to eradication of leukemia blasts escaping the preparative regimen and to clearance of residual host dendritic cells and T lymphocytes (thus preventing graft-versus-host disease and graft rejection, respectively). Improved prevention of graft-versus-host disease might be achieved by redirecting to lymph nodes adoptively transferred, alloreactive NK cells by inducing CCR7-uptake in vitro. Recent studies suggested that, after immune-suppressive therapy, alloreactive NK cells from an HLA-haploidentical donor may prevent leukemia recurrence also in patients who have not received allogeneic hematopoietic stem cell transplantation.
| Original language | English |
|---|---|
| Pages (from-to) | 764-771 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 117 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jan 20 2011 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
Killer Ig-like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation. / Moretta, Lorenzo; Locatelli, Franco; Pende, Daniela; Marcenaro, Emanuela; Mingari, Maria Cristina; Moretta, Alessandro.
In: Blood, Vol. 117, No. 3, 20.01.2011, p. 764-771.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Killer Ig-like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation
AU - Moretta, Lorenzo
AU - Locatelli, Franco
AU - Pende, Daniela
AU - Marcenaro, Emanuela
AU - Mingari, Maria Cristina
AU - Moretta, Alessandro
PY - 2011/1/20
Y1 - 2011/1/20
N2 - Natural killer (NK) cells are key members of the innate immune system. In a self-environment, they sense and kill target cells lacking major histocompatibility complex class I molecules and release various cytokines on activation. The discovery of human leukocyte antigen (HLA) class I specific inhibitory receptors (including the allotype-specific killer immunoglobulin-like receptors), and of various activating receptors and their ligands, provided the basis for understanding the molecular mechanism of NK-cell activation and function, mainly resulting from the balance between activating and inhibitory signals. In an allogeneic setting, such as T cell-depleted haploidentical hematopoietic stem cell transplantation, NK cells may express inhibitory killer immunoglobulin-like receptors that are not engaged by any of the HLA class I alleles present on allogeneic cells. Such "alloreactive" NK cells greatly contribute both to eradication of leukemia blasts escaping the preparative regimen and to clearance of residual host dendritic cells and T lymphocytes (thus preventing graft-versus-host disease and graft rejection, respectively). Improved prevention of graft-versus-host disease might be achieved by redirecting to lymph nodes adoptively transferred, alloreactive NK cells by inducing CCR7-uptake in vitro. Recent studies suggested that, after immune-suppressive therapy, alloreactive NK cells from an HLA-haploidentical donor may prevent leukemia recurrence also in patients who have not received allogeneic hematopoietic stem cell transplantation.
AB - Natural killer (NK) cells are key members of the innate immune system. In a self-environment, they sense and kill target cells lacking major histocompatibility complex class I molecules and release various cytokines on activation. The discovery of human leukocyte antigen (HLA) class I specific inhibitory receptors (including the allotype-specific killer immunoglobulin-like receptors), and of various activating receptors and their ligands, provided the basis for understanding the molecular mechanism of NK-cell activation and function, mainly resulting from the balance between activating and inhibitory signals. In an allogeneic setting, such as T cell-depleted haploidentical hematopoietic stem cell transplantation, NK cells may express inhibitory killer immunoglobulin-like receptors that are not engaged by any of the HLA class I alleles present on allogeneic cells. Such "alloreactive" NK cells greatly contribute both to eradication of leukemia blasts escaping the preparative regimen and to clearance of residual host dendritic cells and T lymphocytes (thus preventing graft-versus-host disease and graft rejection, respectively). Improved prevention of graft-versus-host disease might be achieved by redirecting to lymph nodes adoptively transferred, alloreactive NK cells by inducing CCR7-uptake in vitro. Recent studies suggested that, after immune-suppressive therapy, alloreactive NK cells from an HLA-haploidentical donor may prevent leukemia recurrence also in patients who have not received allogeneic hematopoietic stem cell transplantation.
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U2 - 10.1182/blood-2010-08-264085
DO - 10.1182/blood-2010-08-264085
M3 - Article
VL - 117
SP - 764
EP - 771
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -