In vivo induction of CD4+ T cell responses by antigens covalently linked to synthetic microspheres does not require adjuvant

Macrophages, dendritic cells or B lymphocytes have been shownto play a major role in the presentation of soluble antigensto CD4⁺ T cells. In contrast, the capacity of these cells topresent particulate antigens such as bacterial or parasiticantigens to T cells remains controversial. To investigate thisquestion, well defined particulate antigens were prepared bycovalent linkage of proteins or peptides to 1 µm in diametersynthetic microspheres. The T cell immunogenicity of such particulateantigens was analyzed in vitro and in vivo. In vitro, a solubleprotein such as hen egg lysozyme (HEL) coupled to beads stimulateda strong proliferative T cell response of lymph node cells fromHEL-primed mice or of specific T cell hybridomas. HEL coupledto beads was presented to the specific T cell hybridomas bysplenocytes or by peritoneal macrophages, but not by lymphomaB cells. Immunization of mice with several different proteinantigens or with a synthetic peptide covalently linked to beadsinduced strong CD4⁺ T cell responses in the absence of adjuvant.The strong in vivo immunogenicity of proteins coupled to beadsdid not result from a non-specific adjuvant effect of beadssince covalent linkage of the antigen to beads was strictlyrequired to induce T cell responses in the absence of adjuvant.In vivo treatment by carrageenan showed that macrophages arerequired for the in vivo stimulation of T cell responses bythese particulate antigens. Thus, these results demonstratedthe role of phagocytic cells, especially macrophages, for invivo presentation of particulate antigens. These particulateantigens represent an interesting approach for the developmentof new vaccines, and for the in vivo analysis of the role ofvarious antigen presenting cells in T cell activation and differentiation.     

Antigen Presentation By Class I Major Histocompatibility Complex Molecules: A Context for Thinking About HLA-G

PROBLEM: There is substantial data that support the efficacy of paternal leukocyte immunization (PLI) for the treatment of alloimmune mediated miscarriage; however, there is confusion regarding the laboratory test that should be performed to determine levels of maternal anti-paternal leukocyte antibodies (MAPLA). METHOD: Popular methodologies employed include: 1) microcytotoxicity (MCX), 2) mixed lymphocyte culture (MLC), and 3) cell flow cytometry crossmatch (FCXM). Cell flow cytometry crossmatch correlates well with the more difficult MLC assay although the former proves the more sensitive study. This work compares the MCX assays with FCXM. The study group consisted of ten women who had a history of three or more spontaneous abortions (SABs). All ten had very low levels (<10%) of MAPLA as measured by FCXM. Following PLI all subjects demonstrated elevated levels (>50%) of MAPLA by FCXM. At 12 weeks gestation, sera were simultaneously measured for MAPLA by MCX and FCXM. RESULTS: Although all ten patients had very high levels of MAPLA by FCXM during pregnancy, five of ten had antibodies to HLA Class I and two of ten had antibodies to HLA Class II paternal antigens by MCX. Furthermore, all patients who were positive by MCX to paternal Class I antigens were also positive to Class I antigens not seen in either parent. Both patients who were positive by MCX to paternal Class II antigens were also positive to maternal Class II antigens. Notable is that all ten women eventually delivered healthy infants. CONCLUSION: Based on this preliminary study, the MCX assay is neither sensitive or reliable enough to determine the need and/or to monitor the effectiveness of PLI. Flow cytometry should be the modality of choice when determining the need for alloimmunotherapy and to monitor the effectiveness of treatment.     

树突状细胞的移行与递呈抗原作用的实验研究

借助异硫氰酸荧光素（ＦＩＴＣ）的可显示性，将其作为抗原免疫ＣＢＡ小鼠，以观察树突状细胞的移行及其抗原递呈方式与功能。结果表明，经ＦＩＴＣ两次刺激后（皮内），移行至局部淋巴结的树突状细胞数明显高于对照组（Ｐ＜０．０５）。ＦＡＣＳ的分析结果亦表明，局部淋巴结内的树突状细胞荧光阳性率显著增高，且荧光显微镜观察呈现不均一的膜荧光，提示该细胞的抗原递呈方式为单纯膜结合型，而无内在化过程。ＣｏｎＡ刺激的淋巴细胞增殖反应及ＦＩＴＣ特异性刺激的细胞增殖反应则分别体现了树突状细胞抗原递呈作用的后效应。     

Medical management of chronic pancreatitis

慢性胰腺炎的临床表现包括疼痛、脂肪泻和糖尿病。在西方国家，慢性胰腺炎最常见的病因是酗酒。70％以上的病人在就诊时有疼痛的临床表现，而且，这些患者中又有75％以上会在几年之后出现疼痛减轻或完全消失。对于所有的慢性胰腺炎的病人来说，均应排除非胰源性疼痛和胆道梗阻、胰腺假性囊肿等胰腺局部并发症。应建议所有慢性胰腺炎病人戒烟、戒酒。阿片类镇痛剂仅应用于治疗疼痛严重的病人。尽管有报道认为胰酶替代治疗有助于止痛，但是，对于已经确诊的慢性胰腺炎病人来说，该疗法无效。激素类药物进行腹腔神经丛阻滞术可能有助于病人度过剧烈疼痛期。顽固性疼痛是进行胰液引流或胰腺切除的适应证。建议应用适量胰酶替代联合(或不联合)制酸剂治疗营养不良。慢性胰腺炎导致的糖尿病与原发性糖尿病的治疗原则相似。     

GASTRIC CANCERS IN SINGAPORE: POOR PROGNOSIS ARISING FROM LATE PRESENTATION

Background : Mortality rates from gastric cancer, apart from those derived from Japanese series, remain poor. This paper sought to determine the present outcome of gastric carcinoma in a predominantly Chinese population in Singapore. Prognostic factors useful in predicting survival were also evaluated in this population. Method : All cases of histologically confirmed gastric adenocarcinoma presenting in 1992 were entered into a prospective database. Prognostic factors related to age, sex, site of disease, depth of invasion, histological grade, nodal status and stage of disease were evaluated in patients with resectable disease to determine their utility in predicting survival. Results : Of 1310 consecutive patients with histologically proven adenocarcinomas, 37% had distant metastases at presentation predominantly in the liver (21%) and peritoneal cavity (20%). Sixty-four per cent of patients underwent surgery and in only 51% of these patients was resection of the turnour possible. Stages 111 and IV (T4N2) locally advanced disease were present in 38% of patients. Thus the majority of patients presented with late or metastatic disease (75%, stages 111 and IV). Sixty per cent of patients were alive at I year and 40% at 2 years after resection of the tumour (Kaplan-Meier survival plots). In contrast, no patient survived longer than a year if the tumour was not resectable (P < 0.001, log-rank test). Median survival of patients without surgery was 12 weeks. Median survival for patients with resected stage IV disease was 23 weeks, compared to 18 weeks after surgical bypass. Age, sex, site, depth of invasion and histological grade did not significantly predict survival. Patients with node-negative disease survived longer (2 year, 70%) than those with nodal involvement (2 years, 44%; P = 0.06, log-rank test). Pathologic staging with the TNM system was useful in predicting survival (P < 0.001). Sixty per cent of patients with stage I and II disease were alive at 2 years compared to 54% with stage III disease and 0% with stage IV disease. Conclusion : The prognosis of stomach cancer remains poor, due predominantly to late presentation. Pathologic TNM staging and nodal status were useful in predicting survival outcome after resection. If the tumour were resectable, survival was appreciable even in patients with advanced stage III (2 years, 54%) and stage IV (1 year, 40%) disease. Strategies to improve outcome should focus on early detection of gastric carcinomas.     

Competitive dissociation of encephalitogenic complexes between antigen presenting cells and myelin basic protein

Splenic T cells from myelin basic protein (MBP)-immunised Lewis rats were activated to transfer experimental autoimmune encephalomyelitis (EAE) by co-culture with MBP-pulsed lymphoid dendritic cells (DC). MBP-pulsed DC could be kept for at least 24 h at 37 degrees C in antigen-free medium without affecting their ability subsequently to activate encephalitogenic T cells. However, MBP-pulsed DC were rendered much less stimulatory after a 6 h, but not 2 h, secondary incubation with ovalbumin. Thus, although encephalitogenic complexes between MBP and DC appear very stable in the absence of competing antigens, in their presence, antigen exchange can take place over a period of a few hours; this has positive implications for therapy of EAE by antigen competition.     

小儿重肾31例分析

目的　探讨小儿重肾的诊断及治疗。方法　对我院 1989～ 2 0 0 1年收治的 3 1例小儿重肾进行回顾性分析。结果　 3 1例中有 2 3例患儿接受 2 6次手术 ,有 16例行上半重肾及输尿管切除 ,其中有 2例须处理输尿管残端及盲袋所致的梗阻。 2 2例手术后恢复较好 ,仅 1例伴有轻度的尿失禁。结论　对于重肾伴肾积水或发育不良所致的各种临床表现应首先考虑做上半肾及输尿管大部切除术。B超、CT及静脉肾盂造影术 (IVP)对诊断分型有意义。     

肿瘤微环境对树突细胞功能状态的影响

目的：探讨肿瘤细胞分泌的可溶性细胞因子营造的微环境对树突细胞(DCs，dendritic cells)的分化发育的影响，以进一步揭示肿瘤的免疫逃逸机制。方法：用免疫磁珠从人外周血分离CD14^ 单核细胞，加入粒细胞巨噬细胞集落刺激因子(GM-CSF)、白细胞介素4(IL-4)和人白血病细胞Jurkat培养上清液体外培养DCs，以正常培养诱导的DCs作为对照，采用傅立叶变换红外光谱(FTIR)技术分析人白血病细胞培养上清液对DCs分化发育的影响。结果：正常培养DCs与肿瘤上清液培养的DCs相比，在细胞内蛋白质和核酸的相对含量和细胞内消耗葡萄糖重新合成磷脂的量方面差异无显著性，但是，在细胞的转录状态方面差异有显著性。结论：肿瘤细胞上清液培养液所营造的微环境细胞转录水平上对DCs的功能状态有明显的抑制作用。     

增强抗原呈递功能的树突状细胞疫苗

树突状细胞（DC）疫苗的研究已成为当前肿瘤免疫治疗的一大热点。随着对DC的不断认识，其强大的功能可塑性为发展增强其抗原呈递功能的DC疫苗提供了新思路，现就DC疫苗增强其抗原呈递功能的种种途径进行综述。