RESUMO
The advanced technology microwave sounder (ATMS) onboard the Suomi National Polar-orbiting Partnership (SNPP) satellite is a total power radiometer and scans across the track within a range of ±52.77° from nadir. It has 22 channels and measures the microwave radiation at either quasi-vertical or quasi-horizontal polarization from the Earth's atmosphere. The ATMS sensor data record algorithm employed a commonly used two-point calibration equation that derives the earth-view brightness temperature directly from the counts and temperatures of warm target and cold space, and the earth-scene count. This equation is only valid under Rayleigh-Jeans (RJ) approximation. Impacts of RJ approximation on ATMS calibration biases are evaluated in this study. It is shown that the RJ approximation used in ATMS radiometric calibration results in errors on the order of 1-2 K. The error is also scene count dependent and increases with frequency.
RESUMO
Dendritic cells (DCs) classically promote immune responses but can be manipulated to induce antigen-specific hyporesponsiveness. It has been shown that phenotypically "immature" DCs, defined by low levels of costimulatory molecules at the cell surface, are involved in the induction of peripheral immune tolerance in autoimmunity. Paecilomyces hepiali Chen (PHC) mycelium, as a substitute for Cordyceps, has been used extensively as an immunomodulator to treat numerous diseases. In this study, the effects of an ethanol extract of PHC (EEPHC) on the phenotypic and functional maturation of bone marrow-derived DCs (BM-DCs) from NOD mice were evaluated. EEPHC significantly suppressed the expression of major histocompatibility complex (MHC) class II molecules and the costimulatory molecules CD40 and CD86 in NOD BM-DCs. These DCs also exhibited impaired production of the proinflammatory cytokine interleukin-12 (IL-12) and poor stimulatory capacity in the presence of EEPHC. Moreover, inhibition of the activation and differentiation of cultured DCs was associated with reduced DNA binding activity of nuclear factor kappa B (NF- kappaB), a transcription factor recently shown to be responsible for DC maturation. Administration of 3x10(5) EEPHC-treated DCs into NOD mice aged 3-4 weeks effectively prevented the onset of diabetes. Furthermore, splenocytes from the protected mice produced high amounts of IL-4 and IL-10 and low levels of IL-2 and interferon gamma, suggesting that these DCs deficient in NF- kappaB activity are responsible for the apparent shift in type 2 helper T cells. These novel results showed that EEPHC could specifically inhibit NF- kappaB activity and maintain DCs in a potentially tolerogenic state, permitting their use in strategies to induce immune tolerance in type 1 diabetes.
Assuntos
Células Dendríticas/efeitos dos fármacos , Células Dendríticas/transplante , Diabetes Mellitus Tipo 1/prevenção & controle , Micélio/química , Paecilomyces/química , Animais , Células da Medula Óssea/efeitos dos fármacos , Transplante de Células , Citocinas/biossíntese , Diabetes Mellitus Tipo 1/patologia , Ensaio de Desvio de Mobilidade Eletroforética , Ensaio de Imunoadsorção Enzimática , Etanol , Feminino , Citometria de Fluxo , Genes MHC da Classe II/genética , Indicadores e Reagentes , Camundongos , Camundongos Endogâmicos NOD , NF-kappa B/metabolismo , Fenótipo , Solventes , Linfócitos T Auxiliares-Indutores/fisiologiaRESUMO
OBJECTIVE: To investigate the role of T cell and its subsets in the induction of insulitis and type 1 diabetes mellitus (T1DM) in BALB/c mice. METHODS: Autoimmune diabetes mellitus was developed by intraperitoneal injection of 40 mg/kg streptozotocin (STZ) daily for 5 consecutive days in BALB/c mice as sources of donor cells. Spleen cells from diabetic mice were then cultured for 7 days in the stimulation of interleukin-2 (IL-2) to harvest diabetogenic T cells, which were subsequently transferred into normal BALB/c mice recipients. MTT, ELISA, and HE staining were used to analyze the lymphocyte proliferation, cytokine (IL-2, interferon-gamma, IL-4, and IL-10) levels, and pathological changes in pancreatic islets. RESULTS: As few as 3 x 10(6) diabetogenic T cells successfully induced diabetes mellitus in recipients pretreated with STZ twice, whereas transfer of equal amount of normal splenocytes, T cell-depleted diabetogenic splenocytes, or diabetogenic CD4+ T cells alone in recipients receiving STZ twice pretreatment was proved not to induce diabetes mellitus either. A markedly increased lymphocyte proliferation, high levels of interferon-gamma and IL-2 in the supernatants of diabetogenic T cells were observed. In addition, a markedly enhanced lymphocyte proliferation, a high level of interferon-gamma secretion in serum, and numerous lymphocytes infiltration in pancreatic islets were detected in the diabetic mice induced by diabetogenic T cells transfer. CONCLUSIONS: A novel T1DM murine model is established in STZ-pretreated BALB/c mice by adoptive transfer of diabetogenic T cells. CD4+ T cells with interferon-gamma may promote the onset of diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 1/imunologia , Linfócitos T/imunologia , Animais , Glicemia/metabolismo , Citocinas/imunologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/citologiaRESUMO
The anti-hyperglycemic and immunomodulatory activities of the ethanol extract from Paecilomyces Hepiali Chen (PHC), a Chinese medicine, were investigated in streptozotocin-induced type 1 diabetic (T1DM) mice. Male Balb/c mice, which were i.p. injected with streptozotocin (STZ, 50 mg/kg, for 5 consecutive days) on Day 7, were orally administered saline (the normal control and diabetic control group), Metformin (60 mg/kg, b.w., positive group), or the extract (100 mg/kg, b.w., PHC prevention group) from Day 1 to Day 28, Mice i.p. injected with streptozotocin (STZ, 50 mg/kg, b.w.) for 5 consecutive days prior to PHC treatment (100 mg/kg, b.w.) were used as the PHC treatment group. The effects of PHC on postprandial blood glucose concentrations, plasmatic insulin levels, morphology of pancreatic beta cells and CD4(+) T cells proliferation after 28-day treatment were monitored. Results showed that PHC administered 6 days before STZ induction of diabetes in mice significantly decreased blood glucose level (p < 0.01). An increase of insulin level was also observed as compared to those in the diabetic control group (p < 0.01). In addition, fewer inflammatory cells infiltrated the pancreatic islet and fewer beta cells death by apoptosis within the inflamed islets were observed. More importantly, the CD4(+) T cell proliferation was remarkably attenuated ex vivo in mice preventively treated with PHC (p < 0.01). In comparison to the PHC prevention group, no significant hypoglycemia, changes of insulin level and beta cell protection were observed in mice treated with PHC after STZ administration. Our findings demonstrated that preventive administration of PHC protected beta cells from apoptosis in type 1 diabetes induced by STZ, and the underlying mechanism may be involved in suppressing CD4(+) T cells reaction, reducing inflammatory cells infiltration and protecting beta cell apoptosis in pancreatic islet.
Assuntos
Diabetes Mellitus Experimental/imunologia , Fatores Imunológicos/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Paecilomyces/química , Animais , Apoptose , Glicemia/análise , Linfócitos T CD4-Positivos/citologia , Proliferação de Células , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Masculino , Metformina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , EstreptozocinaRESUMO
Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells (DC) for the induction of peripheral tolerance may be highly relevant. We examined the properties of DC associated with immune suppression in NOD mice by insulin injection subcutaneously and the ability of which to suppress diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. Our data showed that the surface expressions of MHC II and CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice. The dendritic cells with a mature phenotype and increased MLR stimulation adoptively transferred immune tolerogenic effects in secondary NOD-SCID mice, which were associated with significant greater IL-10, TGF-beta production and CD4(+)CD25(+)T differentiation from splenocytes compared with NOD-SCID control recipients. Moreover, treatment with DC remarkably decreased the incidence of diabetes in secondary recipients. These results suggest that a subtype of DC generated by insulin subcutaneous treated NOD mice confers potential protection from diabetes through polarizing the immune response towards a Th2 regulatory pathway.
Assuntos
Células Dendríticas/efeitos dos fármacos , Diabetes Mellitus Tipo 1/prevenção & controle , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Animais , Autoantígenos/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/fisiologia , Citocinas/biossíntese , Feminino , Citometria de Fluxo , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas , Insulina/administração & dosagem , Subunidade alfa de Receptor de Interleucina-2 , Teste de Cultura Mista de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Estado Pré-Diabético/patologia , Estado Pré-Diabético/prevenção & controle , Baço/citologia , Baço/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/fisiologia , Sais de Tetrazólio , TiazóisRESUMO
AIM: To investigate the effect and underlying mechanisms of immune-tolerance induced by the adoptive transfer of bone marrow (BM)-derived dendritic cells (DC) in insulin-dependent diabetes mellitus (IDDM) mice. METHODS: The IDDM model was established by a low dose of streptozotocin (STZ) in Balb/c mice. Two DC subpopulations were generated from the BM cells with granulocyte-macrophage colony-stimulating factor with or without interleukin-4. The purity and the T cell stimulatory capability of DC were identified. These cells were used to modulate autoimmune response in pre-diabetic mice. Blood glucose was examined weekly; pancreas tissues were taken for histopathological analysis, and CD4(+) T cells were isolated to detect lymphocyte proliferation by MTT assay and the ratio of CD4(+)CD25(+) T cells by fluorescence-activated cell sorting (FACS). The cytokine secretion was determined by ELISA analysis. RESULTS: Two DC subsets were generated from BM, which have phenotypes of mature DC (mDC) and immature DC (iDC), respectively. The level of blood glucose decreased significantly by transferring iDC (P< 0.01) rather than mDC. Less lymphocyte infiltration was observed in the islets, and pancreatic structure was intact. In vitro, proliferation of lymphocytes decreased and the proportion of CD4(+)CD25(+) T cells increased remarkably, compared with the mDC-treated groups (P< 0.05), which were associated with increased level of the Th2 cytokine and reduced level of the Th1 cytokine after iDC transfer. CONCLUSION: Our data showed that iDC transfer was able to confer protection to mice from STZ-induced IDDM. The immune-tolerance to IDDM may be associated with promoting the production of CD4(+)CD25(+) T cells and inducing regulatory Th2 responses in vivo.