Human Cytomegalovirus Infection Promotes Rapid Maturation of NK Cells Expressing Activating Killer Ig–like Receptor in Patients Transplanted with NKG2C−/− Umbilical Cord Blood
Mariella Della ChiesaMichela FalcoAlice BertainaLetizia MuccioClaudia AlicataFrancesco FrassoniFranco LocatelliLorenzo MorettaAlessandro Moretta
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NK cells are the first lymphoid population recovering after allogeneic hematopoietic stem cell transplantation and play a crucial role in early immunity after the graft. Recently, it has been shown that human CMV (HCMV) infection/reactivation can deeply influence NK cell reconstitution after umbilical cord blood transplantation by accelerating the differentiation of mature NKG2A(-) killer Ig-like receptor (KIR)(+) NK cells characterized by the expression of the NKG2C-activating receptor. In view of the hypothesis that NKG2C could be directly involved in NK cell maturation driven by HCMV infection, we analyzed the maturation and function of NK cells developing in three patients with hematological malignancies given umbilical cord blood transplantation from donors carrying a homozygous deletion of the NKG2C gene. We show that HCMV infection can drive rapid NK maturation, characterized by the expansion of CD56(dim)NKG2A(-)KIR(+) cells, even in the absence of NKG2C expression. Interestingly, this expanded mature NK cell subset expressed surface-activating KIR that could trigger NK cell cytotoxicity, degranulation, and IFN-γ release. Given the absence of NKG2C, it is conceivable that activating KIRs may play a role in the HCMV-driven NK cell maturation and that NK cells expressing activating KIRs might contribute, at least in part, to the control of infections after transplantation.The haematopoietic system is a classical stem cell hierarchy that maintains all the blood cells in the body. Haematopoietic stem cells (HSCs) are rare, highly potent cells that reside at the apex of this hierarchy and are historically some of the most well studied stem cells in humans and laboratory models, with haematopoiesis being the original system to define functional cell types by cell surface markers. Whilst it is possible to isolate HSCs to near purity, we know very little about the functional activity of markers to purify HSCs. This review will focus on the historical efforts to purify HSCs in humans based on cell surface markers, their putative functions and recent advances in finding functional markers on HSCs.
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食物过敏症是世界范围的一个主要健康问题。桅杆房间在桅杆房间 degranulation 为需要广泛地被学习的立即的超敏性起一个很重要的作用。在这研究，一条途径被采取在 vitro 学习敏化的桅杆房间 degranulation 的特征，它与桅杆房间和动物模型的学习联系了。BALB/c 老鼠被几食物变应原分别地使免疫，然后，血和腹桅杆房间在不同时间点被收集。一颗动态决心在桅杆房间和 serumal IgE 之间被执行。顺序的时间点上的比较分析证明在敏化的 BALB/c 老鼠在桅杆房间 degranulation 和 IgE 抗体 titers 之间有靠近的巧合。而且，敏化的桅杆房间能在 vitro 对挑战实现特定的 degranulation，有趣，但是仔细， tropomyosins 导致了桅杆房间 degranulation 显示的生气反应。这很类似于在 vivo 抵抗变应原的 IgE。学习在桅杆房间上揭示了一些特征，来自敏化的 BALB/c 老鼠，在 vitro 的 degranulation。
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Haematopoietic stem cells (HSCs) can supply all blood cells throughout the adult life of individuals. Based on this property, HSCs have been used for bone marrow and cord blood transplantation. Among various stem cells, HSCs were recognized earliest and were studied most extensively, providing a model for other stem cells. Knowledge of HSC regulation has rapidly accumulated of late. Contributions of scientists in Japan to progress HSC biology are here briefly overviewed. Focusing on the original work accomplished in Japan in the last two decades, people who have led such activities are introduced and their relationships with one another are sketched.
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The action of a toxic substance (P-II fraction), extracted from the pedicellariae of Toxopneustes pileolus, on rat mesentery mast cells was studied. P-II fraction (3×10−5-2×l0−3g/ml) caused a dose-dependent degranulation of mesentery mast cells. The degranulation induced by P-II fraction (10−3g/ml) increased with time, while compound 4 8/80 (1μg/ml) caused a more rapid degranulation. These reactions were dependent on Ca2+ and temperature. When glucose (5.5mM) was omitted during the incubation step, the degranulation by P-II fraction was significantly reduced as compared to that of compound 48/80. On the other hand, the degranulation by P-II fraction was effectively potentiated by the addition of glucose (5.5mM), while the effect of compound 48/80 was unaltered. The effect of theophylline, adrenaline and DSCG on degranulation by P-II fraction or compound 48/80 was compared. In both cases, the degranulation was inhibited by these drugs. These results suggest that P-II fraction-induced degranulation differs from that of compound 48/80 in regards to time course and effects of glucose.
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To produce the wide range of blood and immune cell types, haematopoietic stem cells can “choose” directly from the entire spectrum of blood cell fate-options. Affiliation to a single cell lineage can occur at the level of the haematopoietic stem cell and these cells are therefore a mixture of some pluripotent cells and many cells with lineage signatures. Even so, haematopoietic stem cells and their progeny that have chosen a particular fate can still “change their mind” and adopt a different developmental pathway. Many of the leukaemias arise in haematopoietic stem cells with the bulk of the often partially differentiated leukaemia cells belonging to just one cell type. We argue that the reason for this is that an oncogenic insult to the genome “hard wires” leukaemia stem cells, either through development or at some stage, to one cell lineage. Unlike normal haematopoietic stem cells, oncogene-transformed leukaemia stem cells and their progeny are unable to adopt an alternative pathway.
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Abstract Haematopoietic stem cell transplantation involves the infusion of blood progenitor cells (stem cells) into patients with damaged bone marrow in order to restore normal marrow function. Stem cells may be obtained from a healthy donor (allogeneic) or from the patients themselves (autologous).
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