Primary Alloproliferative TH1 Response Induced by Immature Plasmacytoid Dendritic Cells in Collaboration with Myeloid DCs

The role played by dendritic cell (DC) subsets in the immune response to alloantigens is not well defined. In vitro experiments have extensively shown that freshly isolated myeloid (M)DCs induce a strong T lymphocyte proliferation whereas plasmacytoid (P)DCs do not, unless activated by CD40 ligation. The aim of these studies was to explore whether the interplay among PDCs, MDCs and T cells modulates alloresponse. Freshly isolated MDCs and PDCs were merged in different proportions and used as antigen presenting cells (APCs) in mixed lymphocyte cultures (MLC). As described, isolated PDCs only induced a mild alloresponse, while MDCs were potent inducers of alloproliferation. Unexpectedly, when PDCs were merged with even low numbers of MDCs (down to 100 cells) and used as APCs, a potent Th1 cell proliferation was detected. Survival and maturation of PDCs was increased in these MLC conditions, which could partially explain the magnitude of the T-cell response. Interestingly, the proportion of IFNgamma-producing cells generated in such cultures was higher compared to MDC-stimulated cultures. These data suggest that the interaction between both DC subsets is determinant to generate a potent Th1 response, at least in an allogeneic situation, and may be relevant to the outcome of allogeneic stem cell transplantation.     

Contraception and sexually transmitted diseases: Interactions and opportunities

Today "safe sex" means protection from both unintended pregnancy and sexually transmitted disease and human immunodeficiency virus. These parallel complications of sexual activity have serious biologic and clinical sequelae that should be considered at the time of contraceptive selection. In addition, there is ongoing debate regarding potential interactions between antibiotic intervention and contraceptive steroids. This article assesses the impact of hormonal contraception, spermicides, barrier methods, intrauterine devices, and douching on the pathogenesis of sexually transmitted disease and the human immunodeficiency virus infection. It discusses the direct and indirect effects of contraception methods on clinical physiology and host immune responses while also considering the possible consequences on maternal and infant health if pregnancy results from the use of ineffective contraception. Counseling and care for both family planning and infectious disease protection must be provided to all sexually active individuals. (Ann J OBSTET GVNECOL 1993;168:2033-41.)     

造血干细胞移植后慢性移植物抗宿主病相关的膜性肾病一例

目的 总结造血干细胞移植后慢性移植物抗宿主病（cGVHD）相关的膜性肾病的诊疗体会。方法 为1例急性淋巴细胞白血病患者施行HLA全相合的无关供者外周血造血干细胞移植，术后应用甲氨喋呤和他克莫司（FK506）预防GVHD。术后第19d发生急性GVHD，经甲泼尼龙治疗逆转。分别于术后182d、235d停用FK506和泼尼松，5d后患者出现cGVHD表现，肝功能异常，并伴肾病综合征的相关表现，病理诊断为膜性肾病Ⅱ期，遂给予FK506和泼尼松治疗，同时辅以利尿、降脂等措施。结果发生膜性肾病时，患者的尿蛋白＋＋＋＋，白细胞75个／μl，上皮细胞359．5个／pl，病理性管型＋，管型计数为167个／μl，24h尿蛋白定量为4．28g；肾组织活检，无肾小球硬化，肾小球体积稍大，部分血管袢受压，开放欠佳，肾小球基底膜轻微增厚，外观呈僵硬感，系膜基质轻、中度增殖；间质区部分肾小管扩张，肿胀、变性，未见明显间质纤维化和炎症细胞浸润；Masson染色可见基底膜上皮侧嗜复红物沉积；免疫荧光检查，IgG＋＋＋，C3＋＋＋，IgA＋＋，沿毛细血管袢呈颗粒状节段性分布，系膜区呈团块状分布；IgM、Clq、CA均阴性。电镜下可见肾小球基底膜上皮下沉积物，并有基膜增厚，毛细血管系膜基质轻度增生。经泼尼松和FK506治疗，2个月后尿蛋白转阴。结论 造血干细胞移植后出现肾病综合征或蛋白尿，应考虑GVHD相关膜性肾病的可能，肾穿刺活检有助于诊断，糖皮质激素和FK506治疗有效。     

Characteristics of peripheral blood lymphoid subpopulations of shigellosis patients

Chelyabinsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 3, pp. 299–301, March, 1992.     

Impaired cellular host defence in peritoneal dialysis by two granulocyte inhibitory proteins

Bacterial and fungal peritonitis is associated with a high riskof morbidity and mortality in patients undergoing continuousambulatory peritoneal dialysis (CAPD). Impaired cellular hostdefence in the peritoneal cavity underlies this risk. Two granulocyteinhibitory proteins with a molecular weight of 28000 dalton(GIP I) and about 9500 dalton (GIP II) with homology to light-chainproteins and beta respectively, were isolated from peritonealdialysis effluents. In vitro, both granulocyte inhibitory proteinsinhibit PMNL glucose uptake, phagocytosis and intracellularkilling of bacteria. The IC₅₀ of GIP I or GIP II required forinhibition of half-maximal FMLP-induced or PMA-stimulated PMNLfunction was found to be in the nanomolar range, suggestingvery specific inhibition. These data may explain, at least inpart, defective local cellular host defence in CAPD patients.     

Graft versus graft and graft versus host reactions after HLA-identical bone marrow transplantation in a patient with severe combined immunodeficiency with transplacentally acquired lymphoid chimerism

We describe a patient with severe combined immunodeficiency and transplacental transfer of maternal T cells who received an unfractionated HLA-identical sibling bone marrow transplant without prior conditioning. He presented prior to transplantation with a dermatitis later diagnosed as mild graft versus host disease. He had a normal absolute lymphocyte count, but proliferative responses to mitogens were very low. Antigens of the noninherited maternal HLA haplotype were detected on his blood lymphocytes. After transplantation, he developed a severe reaction including fever, cutaneous erythema and hepatosplenomegaly. Lymphocytes carrying the noninherited maternal HLA haplotype disappeared from his circulation, and his unprimed mononuclear cells became spontaneously cytotoxic to maternal lymphoblasts. He subsequently developed a lymphocytosis of 69,000/mm³, diarrhea, elevated transaminases and a worsening rash, necessitating treatment with immunosuppressive agents. Full T-cell engraftment and evidence of B-cell function later ensued and spontaneously cytotoxic lymphocytes against maternal cells disappeared by 47 days post-transplantation. We postulate that the patient's constellation of signs and symptoms after transplantation represented a combination of severe graft versus graft and mild graft versus host reactions.     

抗CD25抗体预防移植物抗宿主病在儿童白血病半匹配骨髓移植中的应用

目的　探讨抗 CD2 5抗体用于预防儿童白血病半匹配未去 T细胞骨髓移植重度移植物抗宿主病 (GVHD)的疗效。　方法　 10例儿童白血病患者接受 HL A2 - 3位点不合半匹配骨髓移植 ,移植方法除了供者应用粒细胞集落刺激因子 (GCSF)2 5 0μg促进骨髓及受者应用环孢素 A(CSA ) ,甲氨蝶呤 (MTX) ,抗胸腺细胞球蛋白 (ATG)和霉酚酸酯 (MMF)预防 GVHD综合措施外 ,加用抗 CD2 5单克隆抗体预防 GVHD,剂量各为 2 0 m g,在移植前 2 h和移植后第 4天应用 ,采髓后未去 T细胞输注 ,移植结果与前期未用 Simulect移植组比较。　结果　 10例移植后均获造血重建 ,粒细胞大于 0 .5× 10 9/ L 中位天数是19 d,血小板大于 2 0× 10 9/ L 的中位天数是 2 2 d,骨髓植活直接证据检测证实为完全供者造血。无 1例发生急性 ～ GVHD,未用 Sim ulect对照组急性 ～ GVHD为 5 0 % ,差异有显著性意义。可评价慢性 GVHD的 8例均发生慢性 GVHD,均为局限性慢性 GVHD。中位随访 12个月 (范围 9～ 2 4个月 ) ,2例移植相关死亡 ,1例移植后 14个月复发死亡 ,实际无病生存率是 70 % ,与对照比较差异无显著性意义。　结论　本研究儿童半匹配未去 T细胞骨髓移植应用 Sim ulect,明显降低急性重症 a GVHD发生 ,减少移植相关死亡 ,临床应用安全可行。     

慢性移植物抗宿主病相关性肌炎一例

目的总结1例异基因造血干细胞移植后并发与慢性移植物抗宿主病(cGVHD)相关的多发性肌炎的诊治体会。方法1例急性淋巴细胞白血病患者在处于完全缓解状态下接受同胞间供髓异基因造血干细胞移植,移植后采用环孢素A和甲氨蝶呤预防移植物抗宿主病(GVHD)。结果移植后11 d,WBC＞0．5×10~9/L,移植后13 d,血小板＞20×10~9/L；27 d时,骨髓细胞染色体分析显示99%为供者型。移植后17 d,发生Ⅰ度急性皮肤型GVHD,经静脉注射地塞米松及甲氨蝶呤后,GVHD被完全控制。移植后8个月,患者发生轻度肝脏cGVHD,经他克莫司及硫唑嘌呤治疗,效果不佳,血清肝酶升高,后改为他克莫司和西罗莫司治疗,血清肝酶逐渐下降,但肌酸激酶从9 U/L上升至272 U/L,随后患者出现全身乏力,并逐渐加重,上下肢近端处活动出现障碍,肌酸激酶升至3010 U/L,股四头肌、肱二头肌的肌电图表现为肌源性损害,双侧大腿磁共振成像符合多发性肌炎表现,给予甲泼尼龙、血浆置换治疗,但无显著效果,患者突发阵发性呼吸困难,经抢救无效,患者死亡,死亡时肌酸激酶为21 010 U/L。结论多发性肌炎为cGVHD的一种较少见形式,累及重要肌组织者预后较差。     

Inflammation and the Aging Process: Devil or Angel

Inflammation is often viewed as a pathologic mechanism leading to tissue damage and interference with function, such as the process of chronic tissue scarring or fibrosis. However, it is important to note that inflammation is a crucial component of normal tissue repair as well as being fundamental to the body's defense against infection. Considering inflammation as a "causative agent in aging" belies the underlying mechanisms whereby the acute inflammatory response is necessary for survival, and efforts to reduce and control the inflammatory response leave the host susceptible to infectious agents and improper healing. Chronic inflammation inevitably has initiating mechanisms that include immune, autoimmune, and metabolic pathways, leading to the activation and presence of the host-protective response. It is more appropriate to target the underlying initiating conditions than the inflammatory process that ensues and treat the basic mechanisms of disease rather than interfere in a very important protective mechanism of the host.