嗜酸性粒细胞在小鼠体内的抗原呈递过程

目的探讨嗜酸性粒细胞(EOS)在体内能否将抗原呈递给T淋巴细胞,了解EOS在体内呈递抗原的过程和特征.方法以鸡卵清蛋白致敏和雾化吸入刺激BALB/c小鼠以诱发EOS在气道聚集.收集并纯化气道EOS以荧光素标记后注入小鼠气道,应用荧光显微镜观察EOS的移行过程.将接受气管EOS注入小鼠的气管旁淋巴结取出后制备单细胞悬液,以流式细胞仪检测其中T细胞的增殖反应并鉴定增殖T细胞的亚群.结果荧光标记的EOS注入正常鼠气道后8h即可出现于气管旁淋巴结(19.0个/mm2±1.8个/mm2),24h达高峰(59.2个/mm2±7.2个/mm2),并至少可以维持120h(29.6个/mm2±2.8个/mm2).致敏小鼠气管内注入5×105个接触过抗原的EOS1d后气管旁淋巴结增殖的T细胞百分数(6.9%±0.5%)即明显高于基础对照值(3.2%±0.3%,P<0.01),3d后达到峰值(10.8%±0.8%,P<0.01),7d以后下降(6.1%±0.6%,P<0.05).此外,EOS呈递抗原所引起的T细胞增殖反应具抗原特异性,出现增殖反应的T细胞仅限于CD4+细胞.结论气道EOS在体内可成为抗原呈递细胞,从而促使CD4细胞出现显著的增殖反应.     

The effect of intravenous cyclophosphamide pulse on peripheral blood lymphocytes in lupus erythematosus patients

In the present study we investigated the long-term effect of intravenous pulse cyclophosphamide (CY) on lymphocyte surface antigens in systemic lupus erythematosus (SLE) patients. Blood samples derived from 17 lupus erythematosus patients were analysed using two- and three-colour flow cytometry. During the CY therapy, the total number of T lymphocytes (CD3+) was reduced by 31.4%, B lymphocytes (CD19+) by 67.4% and NK cells (CD16+) by 27.4%. Six months after the end of the CY regimen, these values recovered to entry levels. At the onset of the study we observed increased percentages of CD3+ CD25+, CD3+ CD4– CD8–, CD4+ CD29+, CD19+ and CD19+ CD5+ cells. The CY treatment regimen decreased the CD3+ CD25+, CD3+ CD4– CD8–, CD19+ and CD19+ CD5+ cells, but increased the CD3+ CD8+ subpopulation. Taken together, a deficiency of CD8+ T cells associated with CD4+ CD29+ predominance may imply an immune regulatory imbalance leading to abnormal CD4+ cell activation and in consequence to autoimmunity. Depletion of CD19+ cells combined with an enlargement of CD8 cells as a result of CY therapy may reduce the enhanced immune response in SLE patients. Received: 13 December 1996 / Accepted: 10 March 1997     

Alcohol Modulation of Human Normal T-Cell Activation, Maturation, and Migration

We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4⁺ cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and 0-endor-phin pretreatment on the activation of CD4⁺ lymphocytes endowed with the homing receptor CD62L.     

Effect of Immunosenescence on the Induction of Cardiovascular Disease Pathogenesis: Role of Peripheral Blood Mononuclear Cells

It is well established that the immune potential declines with age. However, there is a great paucity of information regarding role of monocytes in elderly suffering from cerebrovascular accident. This present study was undertaken to investigate if the functions of peripheral blood mononuclear cells have any correlation to the manifestation of an age-associated cerebrovascular disorders: myocardial infraction, cerebrovascular (infract & hemorrhage). An age-associated inhibition in the production of interleukin-1 (IL-1) by monocytes was observed while the production of nitric oxide (NO) remained unaltered in the response of monocytes, obtained from normal elderly donors, to Lipopolysaccharide (LPS) treatment in vitro. Cerebrovascular pathologies were found to be associated with an augmentation of IL-1 production by monocyte, while NO production was augmented in case of CVA (hemorrhage) and MI. Trace element copper was found to be lower in the serum of patients suffering from CVA, while concentration of zinc was found to be elevated in serum compared to these trace elements in normal adults. Thus these factors are likely to play a role in the pathogenesis of age-related cerebrovascular disorders.     

Acute Depletion and Recovery of Peritoneal B-1 Lymphocytes in BALB/c Mice after a Single Injection of Mercury Chloride

The acute toxicity of mercury (Hg) to B cells was studied in the peritoneal cavity of BALB/c mice, a coelomic space where both B-1 and B-2 subsets of B lymphocytes are present. Up to 24 hr after a single in situ Hg injection, the peritoneal cavity became virtually devoid of lymphocytes, particularly of the B-1 subset. Lymphocyte depletion was more severe for B than T cells. This depletion was associated with partial lymphocyte activation (CD69⁺) at 6 hr of treatment and it was due to apoptosis rather than to necrosis. Partial recovery of both B and T cells was observed in the peritoneal cavity 48 hr after the Hg injection. The phenomenon was followed by a second decrease in peritoneal lymphocytes 72 hr after Hg. Neutrophils that entered the peritoneal cavity because of the Hg injection were resistant to apoptosis. No significant changes in lymphocyte number or subpopulation were found in the spleen and thymus of the mice up to 72 hr after the Hg treatment. We concluded that B lymphocytes were severely affected by the toxic effects of Hg. Our data suggest that Hg-induced unbalance in the repertoire of B cells, of the B-1 subset in particular, may result later in the secretion of the high titres of pathogenic autoantibodies that are found in the Hg-induced lupus disorder of BALB/c mice.     

Immunomodulatory Activities of HERBSnSENSES™ Cordyceps — in Vitro and in Vivo Studies

The commercially available HERBSnSENSES? Cordyceps (HSCS) belongs to a cultivated strain of Cordyceps sinensis whose immunomodulatory activities has been renowned in traditional Chinese medicine (TCM) for centuries. The present report is the first that describes its immunomodulatory features through a series of in vitro and in vivo experiments. We measured, in peripheral blood mononuclear cells the in vitro effects of HSCS on the gene expression of cytokines and cytokine receptors, cytokine release, and surface expression of cytokine receptors using cDNA expression array, cytometric bead array (CBA), and immunoflorescence staining, respectively, as well as macrophage phagocytosis and monocyte production of H₂O₂ using flow cytometry. Sixty female BALB/c mice were fed with either HSCS (40 mg/kg/day) or water consecutively for 14 days. Proliferation, cytokine liberation, and CD3/4/8 expression of splenic cells were measured using 5-bromo-2′-deoxyuridine proliferation ELISA, CBA, and cytometry immunoflorescence staining, respectively. In vitro results demonstrated that HSCS induced the production of interleukin(IL)-1β, IL-6, IL-10 and tumor necrosis factor alphaα from PBMC, augmented surface expression of CD25 on lymphocytes, and elevated macrophage phagocytosis and monocyte production of H₂O₂. In vivo results showed that HSCS did not induce splenomegaly and cytokine overliberation. Our results possibly provide the biochemical basis for future clinical trials.     

A Toxicokinetic Study of Nickel‐Induced Immunosuppression in Rats

Abstract

The aim of the present study was to investigate dose‐ and time‐dependent effects of NiCl₂ on T‐lymphocyte and macrophage‐derived cytokine production in rats. Moreover we have determined the concentrations of nickel in the plasma that are required to elicit alterations in T‐lymphocyte and macrophage function. NiCl₂ suppressed T‐lymphocyte proliferation and Th1 (IFN‐γ) and Th2 (IL‐10) cytokine production in a dose‐ and time‐dependent fashion. In addition, NiCl₂ inhibited production of the pro‐inflammatory cytokine TNF‐α and increased production of the anti‐inflammatory cytokine IL‐10 from lipopolysaccharide (LPS) stimulated cultures. We have determined that the minimal plasma concentrations of nickel required to provoke immunosuppression are in the range 209–585 ng/mL. In the time‐course study NiCl₂ (3.3 mg/kg) provoked immunological changes that were maximal 1 h following administration, and some of these changes persisted for up to 24 h post administration. Overall these data clearly demonstrate that NiCl₂ suppresses T‐cell function and promotes an immunosuppressive macrophage phenotype in rats. This study also indicates that measuring T‐cell proliferation is as sensitive a marker of NiCl₂‐induced immunotoxicity as measuring T‐cell or macrophage cytokine production. Co‐measurement of circulating nickel concentrations and immune parameters yields valuable information with regard to the potency of nickel to alter immune function in vivo. These data also suggest that quite a large quantity of nickel needs to reach the systemic circulation before any adverse effects on immune function are observed.     

Anti-SRBC Plaque-Forming Cells in Liver,Spleen and Hepatocyte Cell Suspensions of Rabbits and Mice

In a series of experiments in rabbits and mice, we have demonstrated that hepatocytes, isolated at a purity exceeding 98% from immunized animals, possess an immunological activity against the immunizing antigen, sheep red blood cells. Hepatocytes formed hemolyzing plaques as assayed by the Jerne technique, and hepatocyte culture fluids showed both hemagglutinating and hemolyzing activity as well as the presence of immunoglobulin components in immunoelectrophoretic patterns.     

Effect of Moderate Exercise on IgA Levels and Lymphocyte Count in Mouse Intestine

The aim of the present study was to determine the effect of moderate exercise on the production and secretion of IgA in mouse duodenum, on lymphocyte levels in the lamina propria, and on gene expression encoding for cytokines that regulate the synthesis of α-chain of IgA and the expression of pIgR in the lamina propria. Two groups of young Balb/c mice were fed ad libitum, one sedentary and the other with an exercise program (swimming) for 16 weeks. IgA levels in the duodenum were quantified by ELISA; the number of IgA containing cells as well as B cells, CD4⁺ and CD8⁺ T cells in the duodenal mucosa was determined by immunohistochemistry; gene expression was analyzed by real-time PCR, and the expression of proteins by Western blotting. Because of physical training, in the duodenum there was a decrease in the number of IgA producing cells, but an increase in the levels of IgA. Additionally, exercise increased the expression of the genes encoding for IL-4, IL-6, IL-10, TNF-α and TGF β, cytokines that regulate the synthesis of IgA and pIgR, the inflammatory response, and the immune response in the intestine. Thus, the increased IgA found in the duodenal lumen is probably due to the increased production of IgA in the LP and the increased transport of the pIgA-pIgR complex across epithelial cells. Possibly the increased S-IgA levels in the bile also contribute to the change in IgA levels.