嗅鞘细胞移植实验性自身免疫性脑脊髓炎后髓鞘碱性蛋白的表达和小胶质细胞的捕获

目的:研究嗅鞘细胞(OECs)移植实验性自身免疫性脑脊髓炎(EAE)后髓鞘碱性蛋白(Myelin basic protein,MBP)的表达及小胶质细胞捕获OECs情况。方法:用新生近交系Wistar大鼠嗅球培养出OECs,经荧光染料羧基荧光素二乙酸盐琥珀酰亚胺酯(CFSE)标记后注入同系EAE Wistar大鼠侧脑室,免疫组化检测OECs髓鞘碱性蛋白(MBP)、单核巨噬细胞诱导分子1(ED1)和CFSE共表达情况。结果:培养OECs不表达MBP,经侧脑室移植后在EAE大鼠脑内出现多量MBP+CFSE+细胞,同时在大脑广泛区域及血管周围间隙出现多量ED1+CFSE+细胞,与对照组相比差异显著。结论:OECs在EAE环境下表达MBP分子,其抗原能被脑内小胶质细胞或巨噬细胞捕获。     

嗅鞘细胞移植对大鼠实验性自身免疫性脑脊髓炎的影响

目的:探索嗅鞘细胞移植实验性自身免疫性脑脊髓炎(EAE)大鼠的移植途径、可行的移植时间窗,移植后的迁移特性以及发挥保护作用的可能机制。方法:分别采用豚鼠脊髓匀浆(GPSCH)与MOGIgd融合蛋白免疫Lewis大鼠,制作EAE模型;每组发病大鼠分别归入:MOG组和GPSCH组。MOG组分为:OECs空白对照组(MOG0组)4只、OECs尾静脉移植组(MOG1组)7只、OECs侧脑室移植组(MOG2组)4只;GPSCH组分为:OECs空白对照组(GPSCH0组)4只、OECs尾静脉移植组(GPSCH1组)4只。发病高峰期,按照实验分组,分别采用立体定向侧脑室细胞移植和尾静脉细胞移植,观察移植后大鼠的临床症状;移植后2周观察OECs在大鼠体内的分布情况及组织病理学方面的缓解情况。结果:OECs分别经尾静脉、侧脑室移植后,EAE大鼠症状改善,与空白对照组神经功能评分峰差值比较有显著差异(F=18.470,P0.01;t=-7.147,P0.01),MOG1组和MOG2组评分峰差值间无显著差异(P0.05);Hoechst33342示踪证实了OECs能在大鼠体内存活及强大的迁移能力;OECs经尾静脉移植后,可以透过破坏的血脑屏障进入脑内,分布于软脑膜和病灶周围;经侧脑室移植的嗅鞘细胞,向病灶局部广泛迁移;组织病理学评分(HE染色和Luxol fast blue髓鞘染色),移植组与未移植组间无显著差异(P0.05),2种途径移植组间亦无显著差异(P0.05)。结论:纯化培养的成年大鼠嗅球嗅鞘细胞分别经尾静脉和侧脑室移植EAE大鼠,均可缓解发病大鼠的症状。     

耐受性CD8~+ NKT细胞体外增殖能力的鉴定

目的:利用CFSE标记细胞,流式细胞术(FCM)检测法,解析超抗原SEB活化的耐受性CD8+ NKT细胞在体外增殖的情况。方法:利用CFSE标记新鲜分离的C57BL/J鼠脾细胞,分别与ConA和LPS共同培养3d,收集细胞进行荧光染色并用FCM解析细胞表面CD69分子的表达率和增殖能力。CFSE标记的鼠脾细胞与SEB共培养5d和10d后,荧光染色并用FCM解析细胞表面CD69的百分数和增殖能力。SEB活化的第10天细胞经CFSE标记后在IL-2的协同作用下继续培养10d,荧光染色,FCM解析这群细胞的增殖能力、活性分子CD69的表达率和NKT细胞亚群的变化情况。结果:ConA、LPS和SEB三者均可以刺激小鼠脾细胞增殖。ConA和LPS在3d内可以使细胞增殖3代,且CD69的表达率为74.19%和41.56%;SEB在5d和10d内分别可以使细胞增殖5代和7代,细胞表面CD69的表达率为32.09%和48.66%。SEB活化的10d细胞可以在IL-2的协同下继续传代培养10d,可以增殖7代;这群细胞中CD8+ NKT细胞亚群,由原始的0.36%增加到38.58%;细胞表面CD69分子由正常值的0.11%提高到83.74%。结论:超抗原SEB活化的CD8+ NKT细胞可以在体外进行增殖培养,且这些细胞是活性化的细胞。利用CFSE标记细胞,FCM可以检测耐受性CD8+ NKT细胞在体外的增殖水平。     

骨髓间充质干细胞异体移植对小鼠实验性自身免疫性脑脊髓炎的治疗作用

目的探讨大鼠骨髓间充质干细胞(BMSCs)异体移植对小鼠实验性自身免疫性脑脊髓炎(EAE)的治疗作用。方法全骨髓贴壁培养法获得大鼠BMSCs,流式细胞术检测细胞免疫表型,并诱导成骨方向分化。取雌性C57BL/6小鼠,随机分为3组:正常对照组、PBS组和大鼠BMSCs组,用髓鞘少突胶质细胞糖蛋白(MOG)35~55联合完全弗氏佐剂诱导建立EAE模型。小鼠免疫后38d和48d腹腔注射PBS或大鼠BMSCs进行治疗,神经功能评分观察各组小鼠神经功能变化。二次治疗12d后取各组小鼠脊髓、脾脏和外周血。HE染色及Luxol fast blue染色观察脊髓炎性细胞浸润及髓鞘脱失情况;脾脏制成单细胞悬液,细胞CFSE标记后10mg/L刀豆球蛋白(Con A)和MOG_(35~55)刺激培养3d,观察脾细胞增殖情况。ELISA检测大鼠BMSCs移植后外周血细胞因子干扰素γ(IFN-γ)、白细胞介素17(IL-17)含量。结果流式细胞术显示,大鼠BMSCs第3代(P3)细胞表达抗原CD29、CD90、CD106,不表达CD45。体外诱导其能向成骨分化。小鼠发病后,大鼠BMSCs组小鼠神经功能缺损症状较PBS组减轻,评分降低。HE染色和Luxol fast blue染色结果显示,大鼠BMSCs组脊髓炎细胞浸润和脱髓鞘比同时间点PBS组减轻(P0.05)。Con A和MOG_(35~55)刺激培养后,PBS组和大鼠BMSCs组脾细胞增殖增加,而大鼠BMSCs组又较PBS组降低。与PBS组相比,大鼠BMSCs组血浆细胞因子IFN-γ、IL-17含量降低(P0.05)。结论全骨髓贴壁培养法能有效分离纯化BMSCs,大鼠BMSCs异体移植对小鼠EAE模型有治疗作用。     

人骨髓间质干细胞和嗅鞘细胞移植对大鼠急性脊髓损伤功能修复的比较研究

目的对比人骨髓基质细胞(BMSCs)与人胚嗅鞘细胞(OECs)移植对大鼠脊髓损伤功能修复的影响。方法将45只SD大鼠分成脊髓损伤后BMSCs移植组(BMSCs组)、OECs移植组(OECs组)和PBS对照组(PBS组),通过BBB评分、运动诱发电位(MEP)评估脊髓传导功能的改善状况,免疫组织化学方法检测移植细胞存活和分化情况,病理形态学方法观察组织结构修复情况。结果BMSCs组BBB评分高于OECs组(P<0.05);两细胞治疗组MEP潜伏期明显缩短(P<0.05);BMSCs组嗜银染色可见脊髓损伤近端有较多再生纤维向远端延伸,形成神经纤维束,而OECs组再生纤维较少;两种移植细胞均可在损伤处部分存活,BMSCs组可见BMSCs来源的细胞Nestin、NF、GFAP的阳性表达。结论BMSCs移植比OECs移植能更有效促进大鼠急性脊髓损伤修复。     

嗅成鞘细胞移植与甲基强的松龙联合应用对急性脊髓损伤大鼠功能恢复和Nogo-A表达的影响

目的:探讨嗅成鞘细胞(OECs)移植联合应用甲基强的松龙(MP)对急性脊髓损伤大鼠神经功能恢复及Nogo-A表达的影响.方法:自新生SD大鼠嗅球取材,纯化培养嗅成鞘细胞;建立大鼠脊髓挫伤模型,术后1、 3、 7、 14d,参照BBB法进行各组神经功能检测,取脊髓组织,免疫组织化学及RT-PCR法检测Nogo-A表达.结果:OECs组和MP组在7、14d BBB评分高于SCI组,但低于OECs+MP组;免疫组织化学和RT-PCR显示:在3、7、14d,OECs组和MP组Nogo-A的表达量与SCI组相比,均呈明显下调;但其下调Nogo-A效应低于OECs+MP组.结论:OECs移植联合应用MP可明显改善大鼠急性脊髓损伤后神经功能恢复,其机制部分与下调Nogo-A表达有关;OECs移植与MP联合应用在促进SCI后神经功能恢复方面要优于单独使用OECs或MP,两者之间可能存在协同效应.     

胚胎干细胞源性神经前体细胞移植脑缺血大鼠局部细胞的免疫反应

背景：神经前体细胞的免疫原性各家研究结果不一,尤其是体内移植后的机体免疫反应模式需要进一步研究。 目的：体外观察神经前体细胞组成型及诱导型主要组织相容性抗原表达情况;体内观察神经前体细胞移植入大鼠脑缺血组织后局部免疫细胞活化情况,探讨神经前体细胞的移植排斥可能性及模式。 方法：自pCX-hrGFP ES-D3胚胎干细胞诱导分化神经前体细胞,流式细胞术体外检测主要组织相容性抗原Ⅰ,Ⅱ类分子表达及γ-干扰素诱导前后表达变化。实验分3组,磷酸盐缓冲液组、神经前体细胞组分别于大脑中动脉缺血大鼠模型造模后经侧脑室给予磷酸盐缓冲液注射及神经前体细胞移植,假手术组不造模。免疫组化法观察纹状区ED1+、CD4+、CD8+细胞浸润情况;淋巴细胞再刺激增殖实验观测神经前体细胞诱导移植大鼠颈部淋巴细胞的增殖指数。 结果与结论：神经前体细胞组成型高表达主要组织相容性抗原Ⅰ类分子,几乎不表达主要组织相容性抗原Ⅱ类分子;经γ-干扰素诱导后,主要组织相容性抗原Ⅰ类分子进一步上调,主要组织相容性抗原Ⅱ类分子亦有轻度上调,提示神经前体细胞有可能引起机体免疫反应。移植实验表明,与假手术组相比,磷酸盐缓冲液组及神经前体细胞组均表现强烈的ED1+、CD4+、CD8+细胞浸润(P < 0.05),说明脑缺血损伤本身能导致局部免疫细胞活化;神经前体细胞组比磷酸盐缓冲液组有更强的ED1+、CD4+细胞浸润(P < 0.05),提示神经前体细胞移植可能导致局部免疫更进一步活化,且以CD4+T细胞反应为主。磷酸盐缓冲液组及神经前体细胞组神经前体细胞诱导下的增殖指数值均较假手术组升高(P < 0.01),但前两组增殖指数值比较差异无显著性意义(P > 0.05),提示脑组织局部炎症导致颈部淋巴细胞增殖性增加,而离体神经前体细胞不足以单独刺激致敏淋巴细胞增殖。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

负向调节树突状细胞对心脏移植大鼠调节性T细胞的影响

目的:探讨受者树突状细胞(DC)与体外光化学法(PUVA)处理的供者脾淋巴细胞共培养,对心脏移植受者CD4+CD25+调节性T细胞(Treg)及移植心存活时间的影响。方法:以DA大鼠为供者,Lewis大鼠为受者,SD大鼠为无关供者,建立大鼠腹部异位心脏移植模型。分离正常的供者脾淋巴细胞(SP),制备经PUVA处理的供者脾淋巴细胞(PU-VA-SP)。在体外将DA大鼠PUVA-SP或SP与受者骨髓来源的DC共同培养,收集经上述处理后受者DC,流式细胞术(FCM)检测其表面分子CD80、CD86以及OX6的表达状况。根据受者术前静脉输注的成分将实验动物随机分为3组:①Control组:单纯输注PBS,n=7;②SPDC组:输注加载供者SP的受者大鼠DC,n=8;③PUVA-SPDC组:输注加载PUVA处理的供者SP的受者大鼠DC,n=8。移植术前7d,经外周静脉给受者输注与PUVA-SP共培养后的DC(PUVA-SPDC组)、正常受者DC(DC组)或只输注PBS(Control组),移植术后观察受者移植物的存活时间,检测受者外周血中CD4+CD25+T细胞、CD4+CD25highT细胞的比例及其Foxp3表达状况。过继转移PUVA-SPDC组受者大鼠的T细胞后,检测正常LEW大鼠对供者抗原或无关抗原的DTH反应。结果:受者DC与供者未经处理的脾淋巴细胞(SP)混合培养后,其表面分子CD80、CD86以及OX6的表达分别为16.6%±0.72%、36.5%±0.87%及65.6%±1.45%,明显高于未处理DC组(3.53%±0.27%、13.0%±0.57%及27.7%±1.23%)(P0.01);而受者DC与PUVA处理过的供者脾淋巴细胞(PUVA-SP)混合培养后,其表面分子的表达仍保持较低的水平,CD80、CD86以及OX6的表达分别为3.9%±0.12%、13.4%±0.59%及28.0%±1.73%,与未经任何处理的受者DC无统计学差异(P0.05)。移植术后,PUVA-SPDC组受者,外周血CD4+CD25+T、CD4+CD25highT细胞占CD4+T的比例分别是18.97%和3.81%,明显高于输注DC组(4.40%和0.81%)和Control组(3.11%和0.09%)的大鼠(P0.01)。PUVA-SPDC组大鼠外周血CD4+CD25+T细胞中Foxp3表达率为29%±1.73%,CD4+CD25highT细胞中Foxp3阳性率高达95%±1.67%,均明显高于对照组(12%±0.58%和19.3%±2.03%)及DC(16.3%±0.88%和52.0%±1.73%)组(P0.01)。PUVA-SPDC组大鼠移植心存活时间为(27.3±0.98)d,与Control组(6.7±0.29)d及DC组(11.0±0.32)d相比,明显延长(P0.01)。过继转移实验显示,接受PUVA-SPDC组受者T细胞的正常LEW大鼠对DA大鼠抗原的刺激呈特异性免疫低应答状态。结论:PUVA-SPDC能够在移植受者体内诱生CD4+CD25+Foxp3+Treg,同时诱导抗原特异性免疫低反应,进而延长异基因移植物的存活时间。     

肺炎支原体荚膜多糖抑制树突状细胞吞噬和膜分子表达

目的:了解肺炎支原体(Mp)荚膜多糖(CPS)通过结合树突状细胞特异性细胞间黏附分子-3-结合非整合素分子(DC-SIGN)对树突状细胞吞噬功能及细胞表面膜分子表达的影响。方法:复苏培养Mp 菌株,抽提和纯化CPS。培养人外周血单个核细胞来源的DC,吉姆萨染色观察和流式细胞术(FCM)鉴定;用CPS 刺激DC,FCM 检测DC 对FITC-多聚糖的吞噬指数、DC 表面特异标志CD83、HLA-DR 抗原以及协同刺激分子CD80 和CD86 的表达。结果:培养7 d 的DC 有典型的树突状结构,并高表达CD11c 分子。经CPS 刺激后,DC 内FITC-多聚糖的平均荧光强度较对照PBS 处理组显著增加(P<0.05),DC 表面膜分子CD83、HLA-DR、CD80 和CD86 较对照组显著减少(P<0.05)。用CPS 刺激被DC-SING 受体封闭的DC,发现DC 内FITC-多聚糖吞噬指数和四种膜表面分子的表达与对照组差异均无显著性(P>0.05)。结论:Mp CPS 可促进DC 的吞噬功能和减少细胞膜分子CD83、HLA-DR、CD80 和CD86 的表达。     

MOG诱导的实验性自身免疫性脑脊髓炎小鼠中枢及外周神经系统CD4~+ T及CD8~+ T调节性细胞变化

目的:观察实验性自身免疫性脑脊髓炎小鼠中枢及外周CD4+ CD25+调节性T细胞(CD4+ CD25+ Treg),CD8+ CD28-调节性T细胞(CD8+ CD28- Treg)表达的变化情况,并探讨相关的细胞免疫学机制。方法:雌性C57BL/6小鼠随机分为未使用髓鞘少突胶质细胞糖蛋白35-55(MEVGWYR-SPFSRVVHLYRNGK)(MOG35-55)免疫的对照组和使用MOG35-55免疫诱导的EAE小鼠模型组,采用临床症状评分记录小鼠行为学变化、HE染色观察CNS炎症细胞浸润及病理改变,使用流式细胞术(FCM)检测小鼠中枢及外周CD8+ CD28- Treg,CD4+ CD25+ Treg细胞表达水平。结果:MOG35-55诱导的EAE模型组动物出现典型的EAE临床行为学及病理学表现,FCM检测EAE模型组小鼠脾细胞CD4+ CD25+ Treg较对照组升高但无统计学差异,CD8+ CD28- Treg表达水平明显低于对照组(P0.01),EAE模型组中枢有CD4+ CD25+ Treg,CD8+CD28-Treg淋巴细胞的浸润,且CD4+ CD25+ Treg,CD8+ CD28- Treg在中枢的表达均高于外周,对照组中枢神经系统未检测到淋巴细胞浸润。结论:CD4+ CD25+ Treg,CD8+ CD28- Treg均参与调控EAE的病理过程,CD4+ CD25+ Treg,CD8+ CD28- Treg在EAE小鼠中枢及外周分布及变化的不同,提示其进入中枢神经系统(CNS)并参与调节中枢局部炎症。     

Major histocompatibility class I molecules present Urtica dioica agglutinin, a superantigen of vegetal origin, to T lymphocytes.

The Urtica dioica agglutinin (UDA) shares with the superantigens the property of activating T cell subsets bearing particular Vbeta segments of the TCR. However, UDA is a lectin capable of binding to many glycoproteins on cell membranes. The implication of MHC versus other glycoproteins in UDA presentation was presently studied. Using mutant mice lacking MHC class I (MHC-I), MHC class II (MHC-II) or both MHC antigens, we provided evidence that MHC-I and MHC-II molecules serve as UDA receptors. Presentation by either one of these molecules ensured similar T cell responses and co-stimulatory signals were mandatory for optimal T cell activation and proliferation both in MHC-I and MHC-II contexts. Remarkably, in the absence of MHC molecules, UDA could not be efficiently presented to T cells by other glycosylated proteins. Surface plasmon resonance studies were used to confirm the binding of UDA to MHC-I molecules using a fusion protein consisting of MHC-I domains and beta2-microglobulin. The results indicated that the interaction between UDA and MHC-I molecules implicated lectin-binding site(s) of UDA. Taken together, our data demonstrate that, in addition to MHC-II antigens, MHC-I molecules serve as an alternative ligand for UDA.     

Coexpression of intercellular adhesion molecule-1 and class I major histocompatibility complex antigens on hepatocyte membrane in chronic viral hepatitis.

AIMS--To evaluate the role of hepatocyte expression of leucocyte adhesion molecules and major histocompatibility complex (MHC) antigens in the pathogenesis of chronic viral hepatitis. METHODS--The expression of intercellular adhesion molecule 1 (ICAM-1), lymphocyte function associated antigen 3 (LFA-3), and MHC class I and II antigens on hepatocyte membrane in relation to the histological and biochemical activities was studied in patients with chronic B hepatitis, chronic persistent hepatitis (CPH) n = 23; chronic active hepatitis (CAH) n = 20; chronic D hepatitis (CAH) n = 6; and chronic non-A, non-B hepatitis (CPH n = 4, CAM n = 6). Six of the latter were hepatitis C virus antibody positive. RESULTS--In chronic B hepatitis ICAM-1 and MHC-I were expressed significantly more in patients with CAH than in those with CPH (p < 0.001), while the expression of LFA-3 and MHC-II showed no significant difference, irrespective of serum HBeAg or hepatitis B virus DNA. Similar findings were noted in non-A, non-B hepatitis. Regardless of the viral aetiology, patients with CAH had a significantly higher degree of ICAM-1 and MHC-I expression than LFA-3 (p < 0.001 v ICAM-1 and MHC-I, respectively) and MHC-II (p < 0.001 v ICAM-1 and MHC-I, respectively) expression. Those with CPH showed little or no difference in the expression of these four molecules. Furthermore, serum ALT values positively correlated with the hepatocyte expression of ICAM-1 (p < 0.001) and MHC-I (p < 0.001), but not LFA-3 (p > 0.05) and MHC-II (p > 0.05). CONCLUSIONS--In chronic viral hepatitis hepatocyte expression of ICAM-1 and MHC-I might be important for immunosurveillance against virally infected hepatocytes, while the expression of LFA-3 and MHC-II does not seem to have a role in the pathogenesis of chronic viral hepatitis.     

Statins affect cell-surface expression of major histocompatibility complex class II molecules by disrupting cholesterol-containing microdomains

Statins, the main therapy for hypercholesterolemia, are currently considered as possible immunomodulatory agents. Statins inhibit the production of proinflammatory cytokines and reduce the expression of several immunoregulatory molecules, including major histocompatibility complex class II (MHC-II) molecules. In this study, we investigated the mechanism by which simvastatin reduces the membrane expression of MHC-II molecules on several human cell types. We demonstrate that the reduction of MHC-II membrane expression by simvastatin correlates with disruption of cholesterol-containing microdomains, which transport and concentrate MHC-II molecules to the cell surface. In addition, we demonstrate that statins reduce cell-surface expression of other immunoregulatory molecules, which include MHC-I, CD3, CD4, CD8, CD28, CD40, CD80, CD86, and CD54. Our observations indicate that the downregulation of MHC-II at the cell surface contributes to the immunomodulatory properties of statins and is achieved through disruption of cholesterol-containing microdomains, which are involved in their intracellular transport.     

Induction of classical and nonclassical MHC-I on mouse brain astrocytes by Japanese encephalitis virus

Infection with Flaviviruses upregulates the cell surface expression of MHC-I, MHC-II, ICAM-1 (CD54), VCAM-1 (CD106) and TAP proteins. Although all these studies have been confirmed using West Nile virus and other Flaviviruses, there are few reports that have examined the effects of Japanese encephalitis virus (JEV) infection directly on nonclassical and classical MHC expression in astrocytes. We show in this report that JEV infection of mouse brain astrocytes results in induction of the nonclassical MHC Class Ib genes, H-2T23, H-2Q4 and H-2T10 in addition to MHC-I, Type I (alpha/beta) IFNs, TAP-1, TAP-2, Tapasin, LMP-2, LMP-7 and LMP-10 but not IFNgamma, CD80, CD86 and MHC-II genes. The increased cell surface expression of these antigens as well as induction of the genes mentioned above as measured by RT-PCR suggests that JEV infection may lead to the induction of classical MHC Class Ia as well as nonclassical MHC Class Ib molecules.     

PRBAM: a new tool to analyze the MHC class I and HLA-DR anchor motifs

Major histocompatibility complex (MHC) genes are highly polymorphic, which makes each MHC molecule different regarding their peptide repertoire, so they can bind and present to T lymphocytes. The increasing importance of immunopeptidomics and its use in personalized medicine in different fields such as oncology or autoimmunity demand the correct analysis of the peptide repertoires bound to human leukocyte antigen type 1 (HLA-I) and HLA-II molecules. Purification of the peptide pool by affinity chromatography and individual peptide sequencing using mass spectrometry techniques is the standard protocol to define the binding motifs of the different MHC-I and MHC-II molecules. The identification of MHC-I binding motifs is relatively simple, but it is more complicated for MHC-II. There are some programs that identify the anchor motifs of MHC-II molecules. However, these programs do not identify the anchor motif correctly for some HLA-II molecules and some anchor motifs have been deduced using subjective interpretation of the data. Here, we present a new software, called PRBAM (Peptide Repertoire-Based Anchor Motif) that uses a new algorithm based on the peptide–MHC interactions and, using peptide lists obtained by mass spectrometry sequencing, identifies the binding motif of MHC-I and HLA-DR molecules. PRBAM has an easy-to-use interface, and the results are presented in graphics, tables and peptide lists. Finally, the fact that PRBAM uses a new algorithm makes it complementary to other existing programs.     

Adrenal Steroids Modulate the Immune Response during Brucella abortus Infection by a Mechanism That Depends on the Regulation of Cytokine Production

Human brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection with Brucella species. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche for Brucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages in B. abortus infection. Cortisol treatment during B. abortus infection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC-I) and MHC-II expression on the surface of B. abortus-infected monocytes. It is known that B. abortus infection inhibits MHC-I and MHC-II expression induced by gamma interferon (IFN-γ) treatment. DHEA reverses B. abortus downmodulation of the MHC-I and -II expression induced by IFN-γ. Taken together, our data indicate that DHEA immune intervention may positively affect monocyte activity during B. abortus infection.     

Kinetics of the phenotype and function of murine peritoneal macrophages following acute inflammation

This study was undertaken to have a better understand for the process and the underlying mechanisms to limitmacrophage activation and population of activated macrophages.A comprehensive kinetics of cytokineproduction was performed in murine peritoneal macrophages recovered from Balb/c mice at various timeduring the course of an intraperitoneal injection with thioglycollate (TG).The expression of cell surfacemolecules such as MHC-Ⅰ,MHC-Ⅱ,B7-1 and B7-2 of these macrophages were also determined by flowcytometry.The present findings of our research suggested that the population of activated macrophages and theactivation of macrophages (including cytokines production and expression of cell surface functional molecules)were strictly controlled during inflammation process.This is one of the important mechanisms to retain the hosthomeostasis.Cellular & Molecular Immunology.2004;1(1):57-62.     

Phagocytic antigen processing and effects of microbial products on antigen processing and T-cell responses

Summary: Processing of exogenous antigens and microbes involves contributions by multiple different endocytic and phagocytic compartments. During the processing of soluble antigens, different endocytic compartments have been demonstrated to use distinct antigen-processing mechanisms and to process distinct sets of antigenic epitopes. Processing of particulate and microbial antigens involves phagocytosis and functions contributed by phagocytic compartments. Recent data from our laboratory demonstrate that phagosomes containing antigen-conjugated latex beads are fully competent class U MHC (MHC-II) antigen-processing organelles, which generate peptide:MHC-II complexes. In addition, phagocytosed antigen enters an alternate dass I MHC (MHC-I) processing pathway that results in loading of peptides derived from exogenous antigens onto MHC-I molecules, in contrast to the cytosolic antigen source utilized by the conventional MHC-I antigen-processing pathway. Antigen processing and other Immune response mechanisms may be activated or inhibited by microbial components to the benefit of either the host or the pathogen. For example, antigen processing and T-cell responses (e.g. Th1 vs Th2 differentiation) are modulated by multiple distinct microbial components, including lipopolysaccharide, cholera toxin, heat labile enterotoxin of Escherichia coli , DNA containing CpG motifs (found in prokaryotic and invertebrate DNA but not mammalian DNA) and components of Mycobacterium tuberculosis.