ABSTRACT
Abstract Objective To evaluate the frequencies of iNKT cells and their subsets in patients with deep endometriosis. Methods A case-control study was conducted between 2013 and 2015, with 73 patients distributed into two groups: 47 women with a histological diagnosis of endometriosis and 26 controls. Peripheral blood, endometriosis lesions, and healthy peritoneal samples were collected on the day of surgery to determine the frequencies of iNKT cells and subtypes via flow cytometry analysis. Results The authors observed a lower number of iNKT (p= 0.01) and Double-Negative (DN) iNKT cells (p= 0.02) in the blood of patients with endometriosis than in the control group. The number of DN iNKT IL-17+ cells in the secretory phase was lower in the endometriosis group (p= 0.049). There was an increase in the secretion of IL-17 by CD4+ iNKT cells in the blood of patients with endometriosis and severe dysmenorrhea (p= 0.038), and severe acyclic pelvic pain (p= 0.048). Patients with severe dysmenorrhea also had a decreased number of CD4+ CCR7+ cells (p= 0.022). Conclusion The decreased number of total iNKT and DN iNKT cells in patients with endometriosis suggests that iNKT cells play a role in the pathogenesis of endometriosis and can be used to develop new diagnostic and therapeutic agents.
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Objective To analyze the percentage and functional changes of natural killer T (NKT) cells in peripheral blood and bone marrow of severe aplastic anemia (SAA) children before immunosuppressive therapy (IST) comparing to that of healthy children.Methods Ten children with severe aplastic anemia were included in the study and ten healthy children at the same age were selected as the control group. By lfow cytometry, the percentage of CD3+CD1d tetramer+ NKT cell in peripheral blood and bone marrow were detected from March 2014 to December 2014 in our hospital. Immune magnetic bead separation was used to isolate and purify iNKT cells .The puriifed iNKT cells were cultured in the OCH(50 ng/ml,100 ng/ml or 200 ng/ml)+rhIL-2+rhG-CSF culture systems. The ampliifcation of iNKT cells after cultured in different systems were calculated. Elispot method was used to analyze the spotting form cells (SFCs) of IFN-γ or IL-4 expressed by activated iNKT cells.Results The percentage of CD3+CD1d tetramer+ NKT cells in peripheral blood of SAA group(0.72±0.03)% was signiifcantly lower than that of the control group(0.92±0.02)%(P=0.000). The percentage of CD3+CD1d tetramer+ NKT cells in bone marrow of SAA group(0.82±0.02)% was signiifcantly lower than that of the control group(1.05±0.05)%(P=0.000).In vitro iNKT cell ampliif-cation ability of bone marrow in SAA group was signiifcantly lower than the control group, and in medium concentration(50±6) and high concentration OCH group(52±6), the ampliifcation ability was higher than that in low concentration OCH group(30±5) (P<0.05). The secretion of IFN-γ in the iNKT cells of SAA bone marrow was signiifcantly lower in medium concentration(33±3) and high concentration(35±3)OCH group than that of the low concentration(50±3)OCH group(P<0.01). The secretion of IL-4 in the iNKT cells of SAA bone marrow was signiifcantly higher in medium concentration(50±3)and high concentration(75±3) OCH group than that of the low concentration(33±3) OCH group(P<0.01).Conclusions The quantity and function of NKT cells from children with SAA are lower than that of the healthy children.In vitro, they had better ampliifcation ability and could improve IL-4/IFN-γ imbalance in medium concentration and high concentration OCH group than in low concentration OCH group.
ABSTRACT
Invariant natural killer T (iNKT) cells are a unique subset of T lymphocytes that recognize glycolipid antigens presented by the class I-like non-polymorphic histocompatibility complex (MHC) molecule, CD1d. They express both innate and adaptive immune cells’ surface receptors, but act more like cells of the innate immune system. Although iNKT cells represent a relatively small population of T lymphocytes, they can rapidly produce copious amounts of cytokines after activation which can polarize different axes of the immune response. Many glycolipid agonists have been discovered of which the marine sponge-derivative called α-Galactosylceramide (α-GalCer) is a potent ligand for iNKT cells. iNKT cells have been described by many researchers as a critical immunotherapeutic target characterized by having tumor-suppressive potential. However, their actual role in immune responses is still unclear. In addition, the need for appropriate preclinical models that mimic human diseases is important for better understanding the iNKT cell biology. This review describes the characteristics of iNKT cells and their role in immunotherapy in cancers such as multiple myeloma and how they can interact with the components of the neighbouring environment.
ABSTRACT
Sepsis, defined as a systemic inflammatory response syndrome caused by an infection, is a significant cause of mortality worldwide. It is currently accepted that death associated to sepsis is due to an immune hyperactivation state involving the development of a broad proinflammatory response along with alterations in the coagulation system. It is now clear that besides the inflammatory events, the clinical course of sepsis is characterized by the development of an anti-inflammatory response that could lead to death in its attempt to balance the initial response. The purpose of this review is to summarize current mechanisms that explain the pathogenesis of sepsis, underlying the role that cells with immunoregulatory properties play during the course of this complex syndrome. A better understanding of these processes will contribute in the search of more successful therapeutic strategies.
El síndrome de respuesta sistémica consecuencia de una infección, denominado sepsis, constituye una causa significativa de muerte en el mundo. Históricamente se ha aceptado que la muerte por sepsis se debe a un estado de hiperactivación inmunológica, que implica el desarrollo de una vasta respuesta pro-inflamatoria acompañada de alteraciones en el sistema de coagulación. Ahora es claro que además de los sucesos inflamatorios, el curso clínico de la sepsis se caracteriza por el desarrollo de una respuesta anti-inflamatoria que busca contrarrestar la respuesta inicial, y es ésta finalmente en gran parte responsable de la muerte de los pacientes. El propósito de esta revisión es resumir los mecanismos actuales que explican la patogénesis de la sepsis, y específicamente el papel que desempeñan las subpoblaciones celulares con propiedades inmuno-reguladoras durante el curso de la enfermedad. El mejor entendimiento de estos procesos contribuirá a la búsqueda de estrategias terapéuticas más exitosas.