Human natural killer cells in health and disease.

Department of Pediatrics, Columbia University, New York, New York, USA.
Pediatric Blood & Cancer (Impact Factor: 2.35). 11/2007; 49(5):615-23. DOI: 10.1002/pbc.21158
Source: PubMed

ABSTRACT Natural killer (NK) cells are an essential component of the innate immune system and play a critical role in tumor immune surveillance. NK cells express their own repertoire of receptors (NKRs) that bind to major histocompatibility class I or class I-like molecules. The balance of signals from stimulation or inhibition of NKRs determines the ability of NK cells to lyse specific targets. In haploidentical stem cell transplantation with purified stem cells, NK cell alloreactivity (killer immunoglobulin-like receptor [KIR] mismatch) has been demonstrated to reduce the risk of relapse in acute myeloid leukemia. There is a need for adequately powered prospective randomized studies to determine the usefulness of NK cells as adoptive immunotherapy, optimal NK cell doses and timing of administration. Further studies are required to determine optimal selection of donors and recipients, both on NKR matching/mismatching, undergoing haploidentical and unrelated hematopoetic stem cell transplantation.

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    ABSTRACT: Natural killer (NK) cells are essential members of innate immunity and they rapidly respond to a variety of insults via cytokine secretion and cytolytic activity. Effector functions of NK cells form an important first line of innate immunity against viral, bacterial and parasitic infections, as well as an important bridge for the activation of adaptive immune responses. The control of NK-cell activation and killing is now understood to be a highly complex system of diverse inhibitory and activatory receptor-ligand interactions, sensing changes in MHC expression. NK cells have a functional role in innate immunity as the primary source of NK-cell-derived immunoregulatory cytokines, which have been identified in target organs of patients suffering from autoimmune diseases, and play a critical role in early defense against infectious agents. This review focuses on recent research of NK cells, summarizing their potential immunoregulatory role in modulating autoimmunity and infectious diseases.
    Expert Review of Clinical Immunology 07/2009; 5(4):405-20. · 2.89 Impact Factor
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    ABSTRACT: Although reduced natural killer (NK) cell levels have been reported consistently in patients with coronary artery disease (CAD), the clinical significance and persistence of this immune perturbation is not clarified. In this study we characterized the NK cell deficit further by determining (i) differentiation surface markers and cytokine profile of NK cell subsets and (ii) ability to reconstitute NK cell levels over time. Flow cytometry was used to analyse NK cell subsets and the intracellular cytokine profile in 31 patients with non-ST elevation myocardial infarction (non-STEMI), 34 patients with stable angina (SA) and 37 healthy controls. In blood collected prior to coronary angiography, the proportions of NK cells were reduced significantly in non-STEMI and SA patients compared with controls, whereas NK cell subset analyses or cytokine profile measurements did not reveal any differences across groups. During a 12-month follow-up, the proportions of NK cells increased, although not in all patients. Failure to reconstitute NK cell levels was associated with several components of metabolic syndrome. Moreover, interleukin (IL)-6 levels remained high in patients with sustained NK cell deficit, whereas a decline in IL-6 (P < 0·001) was seen in patients with a pronounced increase in NK cells. In conclusion, we found no evidence that reduction of NK cells in CAD patients was associated with aberrations in NK cell phenotype at any clinical stage of the disease. Conversely, failure to reconstitute NK cell levels was associated with a persistent low-grade inflammation, suggesting a protective role of NK cells in CAD.
    Clinical & Experimental Immunology 01/2014; 175(1):104-12. · 3.41 Impact Factor
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    ABSTRACT: INTRODUCTION: NK cells represent a distinct lymphocyte population with extensive cytolytic activity and a variety of other functions, including regulation of hemopoiesis, suppressor functions and immunoglobulin production. Recently, reports suggest that NK cells also display potent regulatory functions via secretion of cytokines or cell-contact-dependent mechanisms. Thus NK cells may regulate innate and adaptive immune responses and play a role in immune homeostasis. AREAS COVERED: NK cells play important roles in viral infections, autoimmunity, pregnancy, cancer and bone marrow transplantation. Although the role of NK cells in allergic diseases is poorly described, recent findings suggest their role in allergy. EXPERT OPINION: Recent developments in the study of NK cell subsets have support their role in allergic diseases that contribute to allergen-specific immune suppression, allergen-specific T(H)1 cell generation as well as IgE and other Ig production.
    Expert opinion on biological therapy 03/2011; 11(7):833-41. · 3.22 Impact Factor

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