Expression of human pim family genes is selectively up-regulated by cytokines promoting T helper type 1, but not T helper type 2, cell differentiation

Cytokines are the most important inducers of T helper (Th) cell differentiation. Interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) are responsible for human Th1-cell differentiation, while IL-4 is the critical cytokine promoting Th2-cell development. These two subsets of cells co-ordinate immunological responses to pathogens as well as autoimmune or allergic reactions. The pim family of proto-oncogenes encodes serine/threonine-specific kinases involved in cytokine-mediated signalling pathways in haematopoietic cells. Here we demonstrate that expression of pim-1 and pim-2 mRNAs is selectively up- or down-regulated in human cord-blood-derived CD4+ cells freshly induced to polarize towards Th1 or Th2 cells, respectively, whereas their expression is inhibited in both cell types by the immunosuppressive transforming growth factor beta (TGF-beta). Moreover, the Th1-specific cytokines IL-12 and IFN-alpha, but not the Th2-specific cytokine IL-4, transiently up-regulate pim-1 and pim-2 mRNA expression in human peripheral blood T cells and natural killer cells. In addition, the Pim-1 protein levels are strongly up-regulated by Th1-specific cytokines in all of these cell types. Taken together, our results suggest that pim genes and their protein products are involved in the early differentiation process of T helper cells.     

Suppressed Cell-Mediated Immunity and Monocyte and Natural Killer Cell Activity Following Allogeneic Immunization of Women with Spontaneous Recurrent Abortion

Spontaneous recurrent abortion (SRA) has been treated by means of immunization with paternal or third-party white blood cells, yet the immunological basis for SRA and for the role of immunization protocols in pregnancy outcome remains controversial. To elucidate this question, nine women with SRA were immunized with paternal mononuclear cells and studied before and 2 weeks after immunization. Seven women who became pregnant gave birth to live newborns. Secretion of the T helper 1 cytokines IL-2 and interferon- by patients' mononuclear cells decreased, while production of IL-10 increased. The levels of natural killer and lymphokine-activated killer cell-mediated cytotoxicity were markedly decreased. Monocyte functions such as secretion of IL-l, tumor necrosis factor a, IL-6, and cytotoxic activity decreased concurrently with elevations in IL-10 and transforming growth factor secretion. Production of IL-12, a pivotal regulatory cytokine, decreased. Furthermore, B7/1 expression on patients' mononuclear cells was downregulated. This resulted in a decrease in monocyte costimulatory activity of purified T cells with soluble anti-CD3, paralleled by a decline in allogeneic proliferative responses. These results suggest that the improved pregnancy success rate in women with SRA following immunization may be partly related to suppression of cell-mediated immunity and monocyte and natural killer cell activity.     

Acute stress reduces intraparenchymal lung natural killer cells via beta-adrenergic stimulation

There are lines of evidence that natural killer (NK) cells are sensitive to physical and psychological stress. Alterations in the immune system including NK cells are known to differ among tissues and organs. The effect of stress on the lung immune system, however, has not been well documented in spite of the fact that the lungs always confront viral or bacterial attacks as well as tumour cell metastasis. In this study, we intended to investigate the effect of restraint stress on lung lymphocytes including NK cells. C57BL/6 mice were exposed to 2 h restraint stress. The concentration of plasma epinephrine significantly rose immediately after the release from restraint as compared to home-cage control mice. Flow cytometric analysis revealed that the numbers of most lymphocyte subsets including NK cells were decreased in the lungs and blood but not in the spleen, immediately after restraint stress. Immunohistochemical examination revealed that the number of NK cells was decreased in the intraparenchymal region of the lungs, while the number of alveolar macrophages did not change. The decrease in the number of NK cells in the lungs and blood was reversed by the administration of propranolol, a nonselective beta adrenergic antagonist. Taken together, our findings suggest that acute stress reduces the number of intraparenchymal lung NK cells via activation of beta adrenergic receptors.     

Immunity and depression: Insomnia,Retardation, and reduction of natural killer cell activity

Depressed patients show a reduction of natural killer (NK) cell activity which may be associated with specific depressive symptoms. The present study demonstrated that sleep disturbance and retardation, but not other depressive symptoms, were negatively correlated with NK activity in 38 depressed patients. Specific behavioral changes in depression such as sleep disturbance and retardation were found to predict 16% of the variance of cytotoxicity levels in depression.     

Antibodies against rabbit red blood cells in murine serum and their effect on the activity of complement alternative pathway

Antibody content against rabbit red blood cells (anti-RaRBC) in murine sera of different strains (Swiss, CBA, C57BL/6, AKR, BALB/c) and activity of complement alternative pathway (AP) were investigated. In contrast to the CBA and C57BL/6, random-bred Swiss strain and inbred BALB/c and AKR strains are good producers of these natural antibodies. There is no correlation between AP activity and anti-RaRBC content. Isolated human anti-RaRBC antibodies, IgM and IgG classes, lead to the enhancement of APhu and APmo activity, contrary to the murine anti-RaRBC which belong solely to IgM class, and do not express this capability.     

Hemopoietic and Lymphoid Progenitor Cells in Human Umbilical Cord Blood

Human umbilical cord blood, which in the past was discarded with the placental tissue, provides a convenient source of fetal hemopoietic cells for scientific analysis and clinical use. Cord blood cells are immature compared to analogous populations in adult peripheral blood. Cord blood B lymphocytes display unique phenotypic and functional characteristics. The antigens CD1C, CD38, CD5, and CD23, although normally expressed on only a small percentage of circulating B cells in adults, are highly expressed on cord blood B cells. Recent studies have demonstrated that whereas cord blood B cells are functionally naive, their potential is similar to that of adult B cells if optimal T-cell help is available. Thus, the failure of B-cell responses in cord blood is due to the T cells. The functional abnormalities of T cells from newborns can be summarized as a dominance of the effects of TH0 cells. Thus, the cytokines produced are immunosuppressive rather than mediating helper activity for B cells. NK activity in cord blood is also depressed compared to that in adults. Cord blood is a very rich source of hemopoietic progenitor cells. The spectrum of progenitors shows a predominance of early progenitor cells when compared with bone marrow. These cells provide an alternative source to adult bone marrow for stem cells to use for hemopoietic reconstitution and as targets in the treatment of hereditary deficiencies by gene therapy. These features make cord blood a unique research tool to investigate hemopoietic ontogeny and a unique clinical tool for transplantation.     

Fibronectin as a compensating factor in the natural cytotoxicity system in interferon-dependent immunodeficiency

The cytotoxicity of natural killer cells (NK) against³H-uridine-labeled target cells (TC, human erythromyeloleukosis cells K-562) and the intensity of conjugate formation in the NK:TC system in the presence of γ-interferon, C-reactive protein, and human fibronectin are studiedin vitro in 14 patients with multiple sclerosis. It is shown that γ-interferon and C-reactive protein decrease the cytotoxic activity of NK with a simultaneous stimulation of conjugate formation in the NK:TC system. The correlation between the studied parameters becomes weaker. Human fibronectin induces collateral changes in the activity of NK and in the number of effector:target conjugates formed in the natural cytotoxicity reaction. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 7, pp. 67–70, July, 1994     

周围神经干自然分束部位血管形态及临床意义

应用微血管灌注透明法观察研究5具成人周围神经干标本.重点观察神经自然分束部位微血管形态和分支分布规律.神经干内有非常完兽的血供系统.手术中循神经自然分束进行追踪分离,不会对神经血供产生明显影响.但在张力下牵拉缝合神经,将对神经干血供产生严重影响.神经束膜缝合比神经外膜缝合更强调在无张力下进行.     

Deficiency of monoclonal antibody (Leu 7) defined NK cells in newly diagnosed insulin-dependent diabetes mellitus

Peripheral blood from 11 newly diagnosed patients with insulin-dependent diabetes mellitus (IDDM) was studied for the proportion of monoclonal antibody (HNK 1, Leu 7) defined natural killer (NK) cells using a fluorescence-activated cell sorter analyzer. The proportion of Leu 7+ cells in patients with IDDM (7.0 +/- 4.0) was significantly (P less than 0.001) lower than in simultaneously studied healthy controls (16.8 +/- 7.0). A 2-yr-old boy with recent onset IDDM had a deficiency of Leu 7+ NK cells (6.1%), while his healthy identical twin had normal proportions of Leu 7+ cells (22.2%), when compared to a simultaneously studied healthy control. Two patients reexamined in remission and one other studied in remission alone, showed deficiency of Leu 7+ NK cells. This study demonstrates a quantitative deficiency of monoclonal antibody (Leu 7+) defined NK cells in newly diagnosed patients with IDDM that persists during remission of the disease and therefore appears to be independent of metabolic abnormality. The deficiency of NK cells may predispose genetically susceptible individuals to viral-induced islet cell injury, contributing to the pathogenesis of IDDM.     

Pregnancy-Associated Uterine Granulated Metrial Gland Cells in Mutant and Transgenic Mice

PROBLEM: Granulated metrial gland (GMG) cells are pregnancy-specific uterine lymphocytes found in rodents. The lineage relationships of GMG cells are incompletely defined, although genetic and immunophenotyping studies suggest membership in the natural killer (NIC) cell lineage. Pregnancy-specific functions have been postulated for GMG cells, but no successful depletion of these cells has been achieved that would permit assessment of any critical roles that might influence gestational outcome. METHOD: Routine histological methods for light microscopy were used to assess implantation sites from wild-type mice and mice of the following genotypes: tgE26, mi/mi, and p53 knockout. RESULTS: GMG cells are transient, histamine-negative cells found in the pregnant uteri of most mice. Pregnancies in the NK and T-cell-deficient tgE26 were characterized by infrequent GMG cells, very small placentae, and an elevated rate of fetal and perinatal mortality. In term placentae of mi/mi with dystocia, GMG cells were found in a new location along the plane of placental separation, and they appeared degranulated. A normal life-history was observed for GMG cells in p53 knockout mice. CONCLUSION: Pregnancies in mutant and transgenic mice indicate that GMG cells are natural killer cells and have critical roles in placental development and pregnancy success. The disappearance of GMG cells at term is independent of p53 gene expression.