49 research outputs found
Evidence for discrete stages of human natural killer cell differentiation in vivo
Human natural killer (NK) cells originate from CD34(+) hematopoietic progenitor cells, but the discrete stages of NK cell differentiation in vivo have not been elucidated. We identify and functionally characterize, from human lymph nodes and tonsils, four NK cell developmental intermediates spanning the continuum of differentiation from a CD34(+) NK cell progenitor to a functionally mature NK cell. Analyses of each intermediate stage for CD34, CD117, and CD94 cell surface expression, lineage differentiation potentials, capacity for cytokine production and natural cytotoxicity, and ETS-1, GATA-3, and T-BET expression provide evidence for a new model of human NK cell differentiation in secondary lymphoid tissues
Pro- and Antiinflammatory Cytokine Signaling: Reciprocal Antagonism Regulates Interferon-gamma Production by Human Natural Killer Cells
SummaryActivated monocytes produce proinflammatory cytokines (monokines) such as interleukin (IL)-12, IL-15, and IL-18 for induction of interferon-γ (IFN-γ) by natural killer (NK) cells. NK cells provide the antiinflammatory cytokine transforming growth factor (TGF)-β, an autocrine/negative regulator of IFN-γ. The ability of one signaling pathway to prevail over the other is likely important in controlling IFN-γ for the purposes of infection and autoimmunity, but the molecular mechanism(s) of how this counterregulation occurs is unknown. Here we show that in isolated human NK cells, proinflammatory monokines antagonize antiinflammatory TGF-β signaling by downregulating the expression of the TGF-β type II receptor, and its signaling intermediates SMAD2 and SMAD3. In contrast, TGF-β utilizes SMAD2, SMAD3, and SMAD4 to suppress IFN-γ and T-BET, a positive regulator of IFN-γ. Indeed, activated NK cells from Smad3−/− mice produce more IFN-γ in vivo than NK cells from wild-type mice. Collectively, our data suggest that pro- and antiinflammatory cytokine signaling reciprocally antagonize each other in an effort to prevail in the regulation of NK cell IFN-γ production
Systemic amyloidosis by LPL
We present the case of an 81-year-old woman with right shoulder discomfort and right supraclavicular lymph node swelling who referred to our hospital. Blood tests results showed normal immunoglobulin levels, but free light chain assay showed abnormal κ/λ ratio. Serum immunoelectrophoresis detected immunoglobulin G-λ type M proteins. 18F-fluorodeoxyglucose computed tomography revealed swelling of the right supraclavicular and mediastinal lymph nodes. Biopsy of the right supraclavicular lymph node showed a mixture of small lymphocytes with plasma cell-like round cells that were positive for cell surface CD20, CD138, CD56, IgG and λ, and negative for transthyretin and amyloid A. They had a Congo red stain-positive, glass-like surrounding structure and apple-green birefringence was observed under polarized light. Duodenal, gastric, and skin biopsies also showed amyloid deposits. We diagnosed the patient with lymphoplasmacytic lymphoma complicated by systemic light-chain amyloidosis. Rituximab monotherapy led to complete metabolic response. Systemic amyloidosis is a rare complication of B-cell lymphoma; however, the possibility of amyloidosis should be considered, even in patients with lymphadenopathy
Polycythemia Vera Terminating in Refractory Ascites
A 64-year-old woman,with more than a 20 year history of polycythemia vera(PV),developed portal
hypertension,myelofibrosis and extramedullary hematopoiesis accompanied by massive ascites. Portal
hypertension resulted not only from infiltration of the liver sinusoids by hematopoietic cells but also from
nodular regenerative hyperplasia of the liver. Wright-stained smears of ascites samples consisted of
mesothelial cells and macrophages. However,cultures of mononuclear cells from the ascites showed the
presence of hematopoietic progenitor cells including megakaryocyte colony formation and burst forming
units. The JAK2-V617F mutation was positive in granulocytes. Contrary to other reports, radiation
therapy was not effective and severe myelosuppression continued for more than one month. We present
the unusual clinical course for this case of PV and discuss the pathophysiology of refractory ascites
Acute Myeloid Leukemia Presenting as Subcutaneous and Epidural Granulocytic Sarcoma Inside and Outside of the Frontal Bone
An 18 year-old male was admitted to our hospital suffering from a large tumor which was located
at the right frontal bone. He was diagnosed to have acute myeloid leukemia (AML) with granulocytic
sarcoma (GS). A chromosomal analysis showed t(8; 21), and a flow cytometric analysis demonstrated
the leukemic cells to be positive for CD56.
Systemic chemotherapy and radiation therapy to the GS, but the patient experienced a relapse in the
lumbar vertebrae. He underwent an umbilical-cord blood stem cell transplantation, however, he died 7
months thereafter. GS is a localized tumor consisting of leukemic myelolasts, which is generally
observed as a complication of either AML, myelodysplastic syndrome, or myelobproliferative disorders.
We herein report this case due to its rarity, even though various sites of GS have been reported