关键词： 协同刺激分子B7-H1   调节性T细胞   结直肠癌   免疫逃逸  

摘要： 目的通过分析人结直肠癌细胞表达B7-H1分子与肿瘤微环境中浸润的调节性T细胞的关系,探讨肿瘤性B7-H1信号参与肿瘤免疫逃逸的机制。方法采用免疫组化分析肠癌组织中B7-H1分子的表达及调节性T细胞的浸润情况,采用细胞培养和流式细胞术分析肿瘤性B7-H1信号对调节性T细胞分化的作用。结果 B7-H1异常高表达在肠癌组织中,正常组织不表达;肿瘤组织中B7-H1表达水平与调节性T细胞浸润数量成正相关(P<0.01),在TGFβ-的共同作用下,M435-B7-H1细胞可以显著促进Tregs的诱导。结论 B7-H1在肿瘤组织异常表达可通过诱导肿瘤微环境中调节性T细胞的分化参与肿瘤免疫逃逸。

关键词： DENDRITIC CELLS   RHEUMATOID-ARTHRITIS   SUPPRESSIVE FUNCTION   IMMUNE-RESPONSES   B10 CELLS   IN-VIVO   INDUCTION   TOLERANCE   ANTIGEN   INTERLEUKIN-10  

摘要： IL-10-producing B cells, also known as regulatory B cells (Bregs), play a key role in controlling autoimmunity. In this study, we report that chimeric mice specifically lacking IL-10-producing B cells (IL-10(-/-) B cell) developed an exacerbated arthritis compared with chimeric wild-type (WT) B cell mice. A significant decrease in the absolute numbers of Foxp3 regulatory T cells (Tregs), in their expression level of Foxp3, and a marked increase in inflammatory Th1 and Th17 cells were detected in IL-10(-/-) B cell mice compared with WT B cell mice. Reconstitution of arthritic B cell deficient (mu MT) mice with different B cell subsets revealed that the ability to modulate Treg frequencies in vivo is exclusively restricted to transitional 2 marginal zone precursor Bregs. Moreover, transfer of WT transitional 2 marginal zone precursor Bregs to arthritic IL-10(-/-) mice increased Foxp3(+) Tregs and reduced Th1 and Th17 cell frequencies to levels measured in arthritic WT mice and inhibited inflammation. In vitro, IL-10(+/+) B cells established longer contact times with arthritogenic CD4(+)CD25(-) T cells compared with IL-10(-/-) B cells in response to Ag stimulation, and using the same culture conditions, we observed upregulation of Foxp3 on CD4(+) T cells. Thus, IL-10-producing B cells restrain inflammation by promoting differentiation of immunoregulatory over proinflammatory T cells. The Journal of Immunology, 2011, 186: 5569-5579.

关键词： T淋巴细胞,调节性   白细胞介素10   淋巴瘤,大B细胞,弥漫性   预后  

摘要： 目的检测FOXP3+调节性T细胞(Treg)及白介素(IL)-10在弥漫性大B细胞淋巴瘤(DLBCL)组织中的表达情况,探讨其与各临床病理因素及预后的关系。方法采用免疫组化SP法,以FOXP3及IL-10为标志物,对69例DL-BCL组织及26例反应性增生的淋巴结和扁桃体进行染色,对阳性细胞分别进行绝对值计数,同时对69例DLBCL患者进行随访。结果 DLBCL中FOXP3+ Treg细胞数目及IL-10+细胞数目与对照组相比,差异具有统计学意义(P<0.01)。FOXP3+ Treg及IL-10+细胞数目在各临床病理因素间差异无统计学意义(P>0.05)。非GC-DLBCL间质中FOXP3+ Treg数目、GC-DLBCL间质中IL-10阳性细胞数目与预后具有相关性(P<0.05)。结论 FOXP3+ Treg与IL-10可作为DLBCL预后因素之一。

关键词： 紫癜性肾炎   过敏性紫癜   白三烯B4   调节性T细胞  

摘要： 目的观察紫癜性肾炎(HSPN)患儿白三烯B4(LTB4)、CD4+CD25+调节性T细胞(regulatory T cell,Treg)表达及其相关性,探讨两者在过敏性紫癜(HSP)肾损害中的作用。方法选择HSP患儿20例,HSPN患儿40例,健康对照者20例。采用ELISA法检测各组血浆LTB4水平,流式细胞术检测各组外周血CD4+CD25+Treg比例,比色法测定24 h尿蛋白(24 hUpro)含量。HSPN患儿中25例行肾组织活检。结果 (1)HSPN组血浆LTB4水平高于HSP组和对照组(P<0.05),HSP组亦高于对照组(P<0.05);(2)HSPN组外周血CD4+CD25+Treg比例低于HSP组和对照组(P<0.05),HSP组亦低于对照组(P<0.05);(3)HSP患儿血浆LTB4水平与CD4+CD25+Treg比例呈负相关(r=-0.74,P<0.05);(4)HSPN组血浆LTB4水平与病理分级、24 h Upro呈正相关(r=0.89,0.91,P<0.01);CD4+CD25+Treg比例与病理分级、24 h Upro呈负相关(r=-0.95,-0.82,P<0.01)。结论 HSPN患儿血浆LTB4水平升高、CD4+CD25+Treg数量减少,二者相互作用参与并促进了HSPN的发生、发展。

关键词： 调节性T细胞   MRL/lpr小鼠   B细胞  

摘要： 目的探讨MRL/lpr小鼠中CD4+CD25+Foxp3+调节性T细胞(Treg细胞)对B淋巴细胞的影响。方法磁珠分选法选出MRL/lpr小鼠及Balb/c小鼠脾脏中的Treg与效应性T细胞(Teff细胞),以尼龙毛柱法分离B细胞;用2种小鼠的Treg细胞分别与MRL/lpr小鼠的B淋巴细胞(加或不加Teff细胞)组成共培养体系,5 d后用酶联免疫吸附法检测上清液中IgA及IgG的水平,计算抑制率;将两种小鼠的Treg细胞注入MRL/lpr小鼠,对照组注入生理盐水,3周后流式细胞法检测小鼠脾脏中CD19+CD27++浆细胞含量。结果两种小鼠Treg细胞对B细胞分泌IgA及IgG均有直接抑制作用,与Teff细胞共培养也能对B细胞IgA及IgG的分泌起抑制作用(总抑制作用),两种小鼠Treg细胞的直接抑制率无显著性差异,总抑制率均大于直接抑制率,且MRL/lpr小鼠的Treg细胞总抑制率显著降低;输注同系Treg细胞的MRL/lpr小鼠,3周后浆细胞的含量显著低于对照组及输入Balb/c小鼠Treg细胞组。结论 Treg细胞可直接或间接抑制MRL/lpr小鼠的B细胞分泌IgA和IgG,MRL/lpr小鼠体内Treg细胞对B细胞的抑制力低于正常对照。输注同系Treg细胞可减少MRL/lpr小鼠浆细胞的生成。

关键词： EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS   BONE-MARROW-TRANSPLANTATION   ANTIGEN-PRESENTING CELLS   IFN-GAMMA   RETINOIC-ACID   TGF-BETA   DEPENDENT MECHANISM   DISEASE LETHALITY   B-CELLS   IMMUNITY  

摘要： Foxp3(+) regulatory T (Treg) cells include thymic-derived natural Treg and conventional T-derived adaptive Treg cells. Both are proposed to play important roles in downregulating inflammatory immune responses. However, the mechanisms of Treg expansion in inflammatory environments remain unclear. In this study, we report that, in an autoimmune-like graft-versus-host disease model of DBA/2 (H-2(d)) donor to BALB/c (H-2(d)) recipients, donor Treg cells in the recipients predominantly originated from expansion of natural Treg cells and few originated from adaptive Treg cells. In vivo neutralization of IFN-gamma resulted in a marked reduction of donor natural Treg expansion and exacerbation of graft-versus-host disease, which was associated with downregulation of host APC expression of B7H1. Furthermore, host APC expression of B7H1 was shown to augment donor Treg survival and expansion. Finally, donor Treg interactions with host APCs via B7.1/B7H1 but not PD-1/B7H1 were demonstrated to be critical in augmenting donor Treg survival and expansion. These studies have revealed a new immune regulation loop consisting of T cell-derived IFN-gamma, B7H1 expression by APCs, and B7.1 expression by Treg cells. The Journal of Immunology, 2011, 186: 2739-2749.

关键词： 四嗪二甲酰胺   慢性B淋巴细胞白血病   CD4+CD25+调节性T细胞   细胞凋亡   流式细胞术  

摘要： 目的研究四嗪二甲酰胺(ZGDHu-1)对慢性B淋巴细胞白血病(chronic B cell lymphocytic leukemia,B-CLL)CD4+CD25+调节性T细胞(regulatory T cells,Tregs)的影响,初步探讨其对CD4+CD25+Tregs的作用机制。方法 B-CLL外周血淋巴细胞分离培养,流式细胞术检测ZGDHu-1作用前后CD4+CD25+/highCD127low、CD19+CD5+以及CD4+CD25+Tregs细胞活力、细胞凋亡、Fas、FasL、APO2.7及Bcl-2、Bax。结果 B-CLL的CD4+CD25+/highCD127low、CD19+CD5+明显高于正常对照组,且CD4+CD25+/highCD127low与CD19+CD5+明显正相关。ZGDHu-1作用后,B-CLL的CD4+CD25+/highCD127low、CD19+CD5+明显降低,CD4+CD25+Tregs活力明显下降和凋亡明显升高;CD4+CD25-T细胞活力也有一定程度的下降,凋亡升高,但其凋亡明显低于CD4+CD25+Tregs。ZGDHu-1作用后,CD4+CD25+Tregs的APO2.7明显增加,Bcl-2明显降低,Bax没有变化,而CD4+CD25-T细胞FasL明显增加。结论 ZGDHu-1作用后B-CLL的CD4+CD25+Tregs明显下降,可能与Bcl-2/Bax比值降低,APO2.7表达增高,而促进B-CLL CD4+CD25+Tregs的凋亡有关。

关键词： 调节性T细胞   T细胞发育   NF-κB   介导   免疫调节功能   免疫耐受   细胞功能   调控作用  

摘要： NF-κB在一种具有维持外周免疫耐受,抑制自身反应性T细胞功能的调节性T细胞（regulatory T cells,Treg）的发育过程中起重要调控作用。自然生成的CD4＋CD25＋Treg通过稳定表达叉头翼状转录因子3（forkhead transcription factor 3,Foxp3）来实现细胞的稳定性和免疫调节功能。

关键词： EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS   PYLORI INFECTION   AFRICAN ENIGMA   CANCER   RISK   MICE   RESPONSES   INTERLEUKIN-10   IL-10   INFLAMMATION  

摘要： B cells regulate autoimmune pathologies and chronic inflammatory conditions such as autoimmune encephalomyelitis and inflammatory bowel disease. The potential counterregulatory role of B cells in balancing pathogen-specific immune responses and the associated immunopathology is less well understood owing to the lack of appropriate persistent infection models. In this paper, we show that B cells have the ability to negatively regulate adaptive immune responses to bacterial pathogens. Using mouse models of infection with Helicobacter felis, a close relative of the human gastrointestinal pathogen H. pylori, we found that B cells activated by Helicobacter TLR-2 ligands induce IL-10-producing CD4(+)CD25(+) T regulatory-1 (Tr-1)-like cells in vitro and in vivo. Tr-1 conversion depends on TCR signaling and a direct T-/B-interaction through CD40/CD40L and CD80/CD28. B cell-induced Tr-1 cells acquire suppressive activity in vitro and suppress excessive gastric Helicobacter-associated immunopathology in vivo. Adoptive cotransfer of MyD88-proficient B cells and Tr-1 cells restores a normal gastric mucosal architecture in MyD88(-/-) and IL-10(-/-) mice in a manner that depends on T cellular, but not B cellular, IL-10 production. Our findings describe a novel mechanism of B cell-dependent Tr-1 cell generation and function in a clinically relevant disease model. In conclusion, we demonstrate that the B cell/Tr-1 cell axis is essential for balancing the control of Helicobacter infection with the prevention of excessive Th1-driven gastric immunopathology, promoting gastric mucosal homeostasis on the one hand and facilitating Helicobacter persistence on the other. The Journal of Immunology, 2011, 186: 878-890.

关键词： 慢性肾功能不全   流式细胞仪   B淋巴细胞   调节性T细胞   益肾降浊冲剂  

摘要： 目的探讨益肾降浊冲剂对慢性肾功能不全(chronic renal insufficiency,CRI)患者B淋巴细胞、调节性T细胞(Treg)的影响。方法 53例CRI患者,根据治疗方案,采用随机数字表法分为治疗组(益肾降浊冲剂)和对照组,以流式细胞仪检测治疗前后慢性肾衰竭患者外周血Treg、B淋巴细胞百分率(CD19+)、活化率(CD19+CD69+)、凋亡率(AV)水平;用CBA流式蛋白分析系统检测外周血细胞因子IL-6、IL-10的水平;用散射速率比浊法测定血清高敏C反应蛋白(hs-CRP);用终点法测定同型半胱氨酸(Hcy);采用贝克曼库尔特血细胞分析仪查血红蛋白含量(HGB);由反相高效液相色谱测定方法测定尿肌酐(UCr);钙(Ca)、磷(P)、尿素氮(BUN)、血肌酐(SCr)、血浆白蛋白(Alb)由BECKMAN-C800全自动生化分析仪测定;根据血Ca、P浓度计算钙磷乘积(Ca×P);根据SCr、UCr和24h尿量计算内生肌酐清除率(CCr)。结果两组治疗后CD19+、CCr水平上升(P<0.01),AV、SCr水平下降(P<0.01),其中治疗组较对照组变化更明显(P<0.05);两组治疗后CD19+CD69+、Treg、IL-6、IL-10、CRP、BUN、P水平及Ca×P无明显变化(P>0.05)。两组治疗后Ca、HGB、Alb均上升(P<0.05),Hcy均下降(P<0.05),但两组比较差异无统计学意义(P>0.05)。相关性分析:CD19+与AV、Hcy呈负相关;AV与ALB呈负相关;SCr与CCr呈负相关,与CRP、BUN呈正相关;CCr与CRP、BUN呈负相关;Hcy与ALB呈负相关;CRP与BUN呈正相关。结论益肾降浊冲剂具有改善肾功能、延缓肾衰竭进展的作用。益肾降浊冲剂通过降低CD19+AV,提高其百分率而对CKD3、4期患者B淋巴细胞具有调节作用。