Hematopoietic Stem Cell Engraftment and Seeding Permits Multi-Lymphoid Chimerism in Vascularized Bone Marrow Transplants

Vascularized bone marrow transplantation (VBMT) across a MHC barrier under a 7-day αβ-TCR mAb and CsA protocol facilitated multiple hematolymphoid chimerism via trafficking of the immature (CD90) bone marrow cells (BMC) between donor and recipient compartments. Early engraftment of donor BMC [BN(RT1ⁿ)] into the recipient BM compartment [LEW(RT1^l)] was achieved at 1 week posttransplant and this was associated with active hematopoiesis within allografted bone and correlated with high chimerism in the hematolymphoid organs. Two-way trafficking between donor and recipient BM compartments was confirmed by the presence of recipient MHC class I cells (RT1^l) within the allografted bone up to 3 weeks posttransplant. At 10 weeks posttransplant, decline of BMC viability in allografted bone corresponded with bone fibrosis and lack of hematopoiesis. In contrast, active hematopoiesis was present in the recipient bone as evidenced by the presence of donor-specific immature (CD90/RT1ⁿ) cells, which correlated with chimerism maintenance. Clonogenic activity of donor-origin cells (RT1ⁿ) engrafted into the host BM compartment was confirmed by colony-forming units (CFU) assay. These results confirm that hematolymphoid chimerism is developed early post-VBMT by T-cell lineage and despite allografted bone fibrosis chimerism maintenance is supported by B-cell linage and active hematopoiesis of donor-origin cells in the host BM compartment.     

Immunomodulatory activity of a pedicellarial venom lectin from the toxopneustid sea urchin,Toxopneustes pileolus

A novel lectin from the large globiferous pedicellariae of the sea urchin, Toxopneustes pileolus, was isolated by a combination of gel chromatography and affinity chromatography techniques. The 32?kDa lectin appeared to have sequence homology to SUL-I, a D-galactose-specific lectin (). This lectin is named SUL-IA. The N-terminal 7 amino acid sequence of SUL-IA was shown to be AVGRSCE. SUL-IA induced mitogenic stimulation on murine splenocytes and T-lymphocytes. SUL-IA also induced chemotaxis for guinea-pig neutrophils and macrophages. In addition, SUL-IA produced IFN-γ in a higher dose range, but not IL-4. These results suggest that SUL-IA may be a biologically functional lectin, which is one of the multiple lectins from the pedicellarial venom of T. pileolus.     

褪黑素对海洛因依赖大鼠淋巴细胞增殖和IL-2产生的影响

目的　观察褪黑素 (MT)对海洛因 (Her)依赖大鼠淋巴细胞增殖和IL 2产生的影响。方法　以剂量递增连续scHer建立海洛因大鼠依赖模型 ,并同时随机设一组给予MT保护。 42d后随机分组 ,设MT治疗组、美沙酮治疗组、自然戒断组、依赖组 ;另选正常大鼠为溶媒对照组。采用MTT法观察MT对ConA诱导的大鼠脾淋巴细胞增殖反应和IL 2的产生。结果　MT保护组 37 5mg·kg-1,bid与依赖组比较 ,对ConA诱导的T淋巴细胞增殖反应和IL 2的产生有明显的促进作用 ;MT 12 5、37 5、6 2 5mg·kg-1,bid 3个剂量组与美沙酮治疗组、自然戒断组比较 ,对ConA诱导的T淋巴细胞增殖反应和IL 2的产生均有不同程度的促进作用。结论　MT对海洛因造成的细胞免疫功能低下可能有预防和逆转的作用。     

Cancer incidence in multiple sclerosis and effects of immunomodulatory treatments

Multiple sclerosis (MS) has been linked to reduced rates of cancer prior to the era of immunomodulating treatments. We assessed the incidence of cancer in a cohort of 1338 MS patients and evaluated the effect of exposure to immunomodulatory treatment. Cancer incidence in the MS population was compared with the expected age- and gender-matched incidence rates in the Israeli population for the period 1960–2003. Time-dependant Cox model analysis was used to estimate hazard ratios for glatiramer acetate, -interferons (1a and 1-b) and intravenous immunoglobulins (IVIg). Among 892 female MS patients, 15 (1.7%) developed breast cancer, and 31 (3.5%) developed cancers of any type. Seventeen of 446 (3.8%) male MS patients developed cancer. The standardized incidence ratios (SIRs) computed until the time of first immunomodulatory treatment were 0.60 (95% CI, 0.38–0.92, p = 0.02) for all female cancer, and 1.11 (95% CI, 0.64–1.91) for all male cancer. Time-dependent covariate analyses for female breast cancer yielded a relative risk for glatiramer acetate of 3.10 (95% CI, 0.86–11.1) and 0.52 (95% CI, 0.07–4.05) for -interferons. For IVIg, the analyses were uninformative. Our findings indicate that cancer incidence is significantly lower in female MS patients than in the general population. Female MS patients treated with glatiramer acetate showed an elevated rate of breast cancer and all MS patients treated with -interferons showed an elevated risk of non-breast cancers though not statistically significant (p = 0.122 and 0.072, respectively). Further study is needed to assess possible associations between long-term exposure to the novel immunomodulatory treatments in MS and rate of caner.     

Anti-inflammatory and immunomodulatory activities of polysaccharide from Chlorella stigmatophora and Phaeodactylum tricornutum

Crude polysaccharide extracts were obtained from aqueous extracts of the microalgae Chlorella stigmatophora and Phaeodactylum tricornutum. The crude extracts were fractionated by ion-exchange chromatography on DEAE-cellulose columns. The molecular weights of the polysaccharides in each fraction were estimated by gel filtration on Sephacryl columns. The crude polysaccharide extracts of both microalgae showed anti-inflammatory activity in the carrageenan-induced paw edema test. In assays of effects on the delayed hyper-sensitivity response, and on phagocytic activity assayed in vivo and in vitro, the C. stigmatophora extract showed immunosuppressant effects, while the P. tricornutum extract showed immunostimulatory effects.     

The Immunological Pregnancy Protective Effect of Progesterone Is Manifested via Controlling Cytokine Production

PROBLEM: This study was aimed at investigating the involvement of an altered cytokine pattern in the immunomodulatory and anti-abortive effects of a progesterone-induced immunomodulatory protein (PIBF). METHOD: PIBF expression on lymphocytes of healthy pregnant women and from women at risk for premature pregnancy termination was determined. In sera of the same women TNFα was quantified by a bioassay using L929 cells. NK activity was determined by a single cell cytotoxicity assay. Cytokine production of the lymphocytes or murine spleen cells was measured by ELISA or detected by immunocytochemistry. In pregnant mice endogenous PIBF activity was neutralized by anti-PIBF IgG. RESULTS: Sera of women at risk for premature pregnancy termination contained significantly higher concentrations of TNFα than those from healthy pregnant women and PIBF expression on the lymphocytes was inversely related to serum concentration of TNFα. Increased NK activity of lymphocytes after neutralization of endogenous PIBF activity is corrected by anti-IL2 treatment and PIBF inhibits IL12 expression on activated lymphocytes. PIBF increases IL-10 production by activated spleen cells. In pregnant mice, neutralization of endogenous PIBF activity by specific antibody results in increased resorption rate and reduced splenic IL-10 production. CONCLUSIONS: Our data allow the assumption that via blocking IL-12 production PIBF inhibits NK activation with a concomitant reduction of TNFα levels. Disturbances in this system might lead to the expression of the known synergistic effect of IL-12 and TNFα, resulting in a Th1 type cytokine dominance and pregnancy termination.     

共轭亚油酸对小鼠免疫功能的影响

研究共轭亚油酸的免疫调节作用。采用正常小鼠及腹腔注环磷酰胺(Cy)造成免疫低下小鼠模型，共轭亚油酸灌胃40d后，用MTT法测脾细胞增殖活性，二硝基氟苯(DNFB)诱发迟发性变态反应(DTH)，测血清溶血素水平(HC50)，测胸腺脾脏指数。共轭亚油酸能显著提高免疫低下及正常小鼠的淋巴细胞增殖水平。可增强免疫低下小鼠迟发变态反应，提高胸腺指数。但对脾脏指数及血清溶血素水平无影响。可见，共轭亚油酸对T淋巴细胞介导的细胞免疫具有一定的免疫调节作用。     

细胞因子风暴及其治疗方法的研究进展

由致病因素激活人体先天性和适应性免疫反应所导致的炎症反应是人体的第一道防线。然而,某些病原体(如SARS-CoV-2、SARS-CoV、MERS-CoV和登革热病毒等)会在宿主内引发威胁生命的"细胞因子风暴",进而引起多器官功能衰竭并最终导致死亡。一些内源性消炎调控因子,如消退素、脂氧素、环氧不饱和脂肪酸等,可以调节组织损伤而不破坏有益的炎症应答,为炎性疾病的治疗提供了新途径。其中可溶性环氧化物水解酶(soluble epoxide hydrolase,sEH)抑制剂可以稳定环氧二十碳三烯酸(epoxyeicosatrienoic acids,EETs),通过多种机制调控细胞因子,重塑机体致炎/抗炎平衡,从而发挥消退炎症的作用,有望成为治疗细胞因子风暴的新靶点。本文综述了细胞因子风暴的病理机制以及目前潜在的治疗方法,希望为相关疾病的诊断和治疗提供新的思路。     

白芍总甙的免疫调节作用及机理

本文报道TGP的免疫调节作用,并探讨其作用机理。TGP 5 mg·kg~(-1)·d~(-1) ip 5～8 d对Cy诱导的小鼠DTH反应增高或降低呈反向调节,也可拮抗Cy诱导的小鼠溶血素生成量下降,表现出双向调节特征。TGP本身无有丝分裂原样作用,但终浓度45和450 ng/ml可促进ConA诱导小鼠脾淋巴细胞的增殖;同样浓度还可促进NDV诱导的人脐血白细胞产生IFNα,TGP的这种免疫增强作用可能是其体内向上恢复免疫功能的机理之一。TGP 5～10 mg·kg~(-1)·d~(-1) ip 4～8 d对DXM抑制小鼠溶血素的生成及DTH反应无明显拮抗作用,同时TGP还可使正常小鼠和DXM处理的SRBC致敏小鼠血浆CS水平下降。     

Current medical therapy of inflammatory bowel disease

The 1990's have brought a significant promise and the hope for a better and brighter future in the new millennium for patients with inflammatory bowel disease (I3D). A better understanding of the pathophysiology of IBD symptoms has led to newer treatnent modalities and streamlining of therapy for specific subsets of patients. ULCERATIVE COUTISThe treatnent for ulcerative colitis (UC) is aimed at modulating the inflammatory response. The drugs which are found to be effective are sulfasalazine (Azulfidine, Salazopyrin) and its 5ASA derivatives, glucocorticosteroids, immunomodulators/immunosuppressants, and other new potential drugs (Table 1).