细胞毒性T淋巴细胞相关抗原4融合蛋白抑制狼疮肾炎患者外周血单个核细胞B7分子表达及抗体产生

目的 探讨细胞毒性T淋巴细胞相关抗原4融合蛋白(CTLA-4Ig)对活动期狼疮肾炎(LN)患者外周血单个核细胞(PBMC)细胞表面B7-1(CD80)和B7-2(CD86)表达的影响及其对抗双链DNA(dsDNA)抗体和免疫球蛋白产生的影响.方法 将18例活动期LN患者的抗凝血标本随机分为LN的CTLA-4Ig处理组(LN-T组9例)和普通培养组(LN-NC组9例).另以14例正常人的抗凝血标本为对照,随机分为正常人的CTLA-4Ig处理组(NC-T组7例)和普通培养组(NC-NC组7例).用密度梯度离心法分离PBMC.处理组加入CTLA-4Ig(10 ng/L)、普通培养组加入等量普通培养基37℃孵育72 h后,采用流式细胞仪技术检测PBMC细胞表面B7-1和B7-2分子的表达;ELISA法检测孵育液中抗dsDNA抗体、IgG及IgM水平.结果 活动期LN患者CTLA-4Ig处理组与普通培养组比较,PBMC表面B7-2分子表达明显下降(P＜0.01);B7-1分子表达无显著变化(P＞0.05);孵育液中抗dsD-NA抗体、IgG及IgM的生成均明显减少(P＜0.01).而正常人的两组间各指标差异均无统计学意义(P＞0.05).结论 CTLA-4Ig可抑制活动期LN患者的PBMC表面B7-2分子的表达,并可减少其抗dsDNA抗体、IgG及IgM的分泌.     

系统性红斑狼疮外周血单个核细胞CD28/B7分子mRNA的表达

目的 :探讨CD2 8 B7分子在系统性红斑狼疮 (SLE)发病机制中的作用及其临床意义。方法 :应用逆转录 聚合酶链反应 (RT PCR)检测 35例活动期SLE患者和 30例正常人外周血单个核细胞 (PBMC)中CD2 8、B7 1和B7 2mRNA的表达水平。结果 :35例活动期SLE患者PBMC中CD2 8的阳性表达率 (2 2 86 % )明显低于正常人对照组 (70 0 0 % ) ,差异非常显著 (P <0 0 0 1) ;B7 2的阳性表达率 (82 86 % )明显高于正常对照组 (5 3 33% ) ,差异显著 (P <0 0 1) ;活动期SLE组CD2 8的平均表达水平 (0 194 5± 0 2 0 74 )明显低于正常对照组 (0 4 2 38± 0 10 5 3) ,差异显著 (P <0 0 5 ) ;B7 2的平均表达水平 (0 86 75± 0 2 5 75 )明显高于正常人对照组 (0 4 898± 0 30 72 ) ,差异非常显著 (P <0 0 1) ;35例活动期SLE患者中仅有 2例B7 1呈阳性表达。结论 :CD2 8 B7分子的异常表达可能与SLE患者淋巴细胞和抗原呈递细胞 (APC)的功能变化有关。B7 1低水平与B7 2的高水平表达表明 ,SLE患者T细胞的活化可能主要是通过CD2 8与B7 2的交联传递共刺激信号 ,介导以Th2型反应为主的免疫应答反应 ;B7 2的表达水平可能与SLE疾病的活动性有一定的相关性。CD2 8mRNA的低水平表达可能与外周血CD2 8 T细胞凋亡增加或迁移到炎症部     

FcγRⅡB1介导的信号传导异常与SLE患者B细胞的过度活化

目的:观察系统性红斑狼疮(SLE)患者B细胞表面功能分子表达的特征及其功能状态,评价以FcγRⅡB1(CD32)为代表的B细胞自身抑制调节机制在SLE发病中的作用。方法:采用Ficoll密度梯度离心法分离出人外周血单个核细胞(PBMC),并以免疫磁珠法(MACS)分离纯化B细胞。采用荧光分光光度法检测B细胞受不同激活物刺激后细胞内钙([Ca2 ]i)的反应。用ELISA法检测B细胞与刺激物共同培养后所分泌IgG的量。采用流式细胞术及间接免疫荧光染色法,检测B细胞膜表面CD32、CD19及IgM的表达水平。结果:(1)以羊抗人μ链的F(ab′)2片段及完整IgG分别刺激SLE患者B细胞时,其[Ca2 ]i反应的比值显著低于类风湿性关节炎(RA)患者(P<0.05)及正常人对照(P<0.01)。(2)分别用葡萄球菌A蛋白(SPA)单独刺激与SPA和羊抗人μ链的完整IgG抗体共同刺激SLE患者的B细胞所分泌的IgG的比值,明显低于RA患者及正常人对照组(P<0.05)。(3)SLE患者与RA患者及正常对照组B细胞上CD19、CD32及IgM的表达无统计学意义(P>0.05)。结论:SLE患者B细胞上CD32抑制性信号传导的异常,可能是导致B细胞过度活化的重要机制。     

CD40在系统性红斑狼疮外周血淋巴细胞的表达

使用密度离心法分离SLE患者和正常人外周血单个核细胞 (PBMC ) ,采用流式细胞术检测B淋巴细胞白细胞分化抗原 4 0 (CD4 0 )的表达水平 ,进行SLE患者 (活动期和缓解期 )和正常人之间的比较 ;并进行B淋巴细胞CD4 0表达水平和血清抗dsDNA抗体水平及狼疮活动指数 (SLEDAI)的相关分析。结果表明 ,活动期SLE患者外周血B淋巴细胞比例 (% )和其表达CD4 0的比例 (% )均明显高于缓解期SLE患者和对照组 ,其表达CD4 0的平均荧光强度 (MFI)在活动期SLE患者最高 ,缓解期SLE患者稍低 ,对照组最低 ;相关分析结果表明 ,活动期SLE患者B淋巴细胞CD4 0的表达比例 (% )和强度 (MFI)均与血清抗dsDNA抗体及SLEDAI呈正相关 ,后两者呈高度相关 ;缓解期SLE患者B淋巴细胞表达CD4 0的强度 (MFI)和SLEDAI呈正相关。CD4 0在活动期SLE患者B淋巴细胞的表达增加 ,其水平与疾病活动度有关。     

系统性红斑狼疮患者外周血单个核细胞NF-κB活性测定及其临床意义

目的研究系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中的NF-κB活化情况并探讨其临床意义。方法采用凝胶阻滞电泳(EMSA)检测NF-κB活性,抗dsDNA抗体及IgG测定使用ELISA方法。结果SLE患者和正常对照组均有一定量的NF-κB活化,但SLE患者NF-κB活性明显高于正常对照组,且活动期又明显高于非活动期。SLE患者NF-κB活化量与SLEDAI及PBMC培养上清液dsDNA、IgG分泌量呈正相关。结论SLE患者体内NF-κB处于高表达状态,NF-κB活化量与疾病活动程度及自身抗体的产生密切相关,阻抑NF-κB过度活化可能有利于SLE的治疗。     

转染人CTLA-4细胞的对树突状细胞B7分子表达的影响

从PHA活化的人外周血T细胞中抽提总RNA,经RT-PCR扩增出CTLA-4的全长基因,构建逆转录病毒载体pEGZ-Term/CTLA-4,经PCR及电泳鉴定后感染包装细胞293T。收集培养上清感染L929细胞。用Zeocin选择培养。经免疫荧光及流式细胞术进行筛选,获取稳定表达CTLA-4分子的细胞株CTLA-4/L929。将CTLA-4/L929经丝裂霉素处理后与体外细胞因子诱导的树突状细胞共同孵育。分别于24、48及72h,用直接免疫荧光法和流式细胞术分析树突状细胞B7-1和B7-2分子的表达。研究结果显示,构建的重组逆转录病毒载体pEGZ-Term/CTLA-4的PCR产物长约700 bp,与人CTLA-4基因的长度一致。经Zeocin选择及多次亚克隆化培养,CTLA-4基因转染细胞CTLA-4/L929稳定表达膜型CTLA-4分子。以其为刺激细胞与树突状细胞共同培养后,可明显下调树突状细胞B7-1的表达,但对B7-2的表达没有影响。本研究获得的CTLA-4基因转染细胞株,为进一步探讨CTLA-4及其配基分子在免疫应答中的作用与机制提供了手段。     

重症肌无力患者外周血B7∶CD28/CTLA4共刺激分子表达的动态变化

目的研究重症肌无力(MG)患者B7∶CD28/CTLA4共刺激通路相关分子表达动态变化及其与MG发病的关系. 方法用流式细胞仪检测18例MG患者和16例健康对照者外周血单个核细胞(PBMC)在经PMA(佛波酯)+ionomycin(钙离子导入剂)刺激的0 h、6 h、24 h、48 h时B7-1、B7-2、CD28、CTLA4分子在CD4+ T细胞和CD8+ T细胞表面的表达. 结果 (1) 0 h,MG患者B7-1、B7-2分子总体表达增加,CD4+、CD8+ T细胞表面B7-1、B7-2的表达未见明显增加,PMA+ionomycin刺激后B7-1、B7-2在CD4+、CD8+ T细胞表面也无增加;(2) 0 h,CD28、CTLA4的表达增强,其中CD28+细胞的增多主要表现在CD4+ T细胞亚群,CTLA4的表达增强主要在CD8+ T细胞,在PMA+ionomycin激活后,CD28表达明显增强,持续到48 h都处于较高水平(与对照组相比P＜0.01),CTLA4表达出现短暂增强,6 h即达高峰,以后下降,与对照组相比无显著增强(P＞0.05). 结论 MG患者外周血中B7∶CD28/CTLA4通路共刺激相关分子表达增高,持续时间延长,检测共刺激分子的表达可反映机体的免疫激活状态,B7∶CD28/CTLA4通路在MG发病中可能起重要作用.     

体外诱导和检测人类B细胞产生抗HLA抗体的研究

目的 体外诱导和采用酶联免疫斑点法(ELISPOT)检测人类B细胞产生的抗HLA抗体.方法 对7名健康志愿者采用密度梯度离心法分离外周血单个核细胞(PBMC)并体外培养5 d,以B细胞多克隆刺激原美洲商陆丝裂原(PWM)、葡萄球菌A蛋白菌体(SAC)体外刺激PBMC,采用EHSA和ELISPOT方法分别测定培养上清中Ig浓度和抗体分泌B细胞数,探索体外诱导PBMC产生Ig的适宜方法.采用该刺激方法和HLA特异的ELISPOT法,诱导和检测9例拟行肾移植预致敏对象PBMC产生的抗HLA抗体.结果 与PWM单刺激相比,PBMC在PWM和SAC联合刺激后,有更多细胞存活的趋势(P=0.052),且培养上清中IgM的水平明显增加(P=0.03),而IgG的水平无明显变化(P>0.05).6例预致敏对象诱导和检测到抗HLA抗体.其特异性与各自培养上清中检测到的抗HLA抗体一致.结论 PWM和SAC体外刺激PBMC,结合HLA特异的ELISPOT方法,能诱导和榆测到人类B细胞产生的HLA抗体.     

体外诱导和检测人类B细胞产生抗HLA抗体的研究

目的 体外诱导和采用酶联免疫斑点法(ELISPOT)检测人类B细胞产生的抗HLA抗体.方法 对7名健康志愿者采用密度梯度离心法分离外周血单个核细胞(PBMC)并体外培养5 d,以B细胞多克隆刺激原美洲商陆丝裂原(PWM)、葡萄球菌A蛋白菌体(SAC)体外刺激PBMC,采用EHSA和ELISPOT方法分别测定培养上清中Ig浓度和抗体分泌B细胞数,探索体外诱导PBMC产生Ig的适宜方法.采用该刺激方法和HLA特异的ELISPOT法,诱导和检测9例拟行肾移植预致敏对象PBMC产生的抗HLA抗体.结果 与PWM单刺激相比,PBMC在PWM和SAC联合刺激后,有更多细胞存活的趋势(P=0.052),且培养上清中IgM的水平明显增加(P=0.03),而IgG的水平无明显变化(P>0.05).6例预致敏对象诱导和检测到抗HLA抗体.其特异性与各自培养上清中检测到的抗HLA抗体一致.结论 PWM和SAC体外刺激PBMC,结合HLA特异的ELISPOT方法,能诱导和榆测到人类B细胞产生的HLA抗体.     

体外诱导和检测人类B细胞产生抗HLA抗体的研究

目的 体外诱导和采用酶联免疫斑点法(ELISPOT)检测人类B细胞产生的抗HLA抗体.方法 对7名健康志愿者采用密度梯度离心法分离外周血单个核细胞(PBMC)并体外培养5 d,以B细胞多克隆刺激原美洲商陆丝裂原(PWM)、葡萄球菌A蛋白菌体(SAC)体外刺激PBMC,采用EHSA和ELISPOT方法分别测定培养上清中Ig浓度和抗体分泌B细胞数,探索体外诱导PBMC产生Ig的适宜方法.采用该刺激方法和HLA特异的ELISPOT法,诱导和检测9例拟行肾移植预致敏对象PBMC产生的抗HLA抗体.结果 与PWM单刺激相比,PBMC在PWM和SAC联合刺激后,有更多细胞存活的趋势(P=0.052),且培养上清中IgM的水平明显增加(P=0.03),而IgG的水平无明显变化(P>0.05).6例预致敏对象诱导和检测到抗HLA抗体.其特异性与各自培养上清中检测到的抗HLA抗体一致.结论 PWM和SAC体外刺激PBMC,结合HLA特异的ELISPOT方法,能诱导和榆测到人类B细胞产生的HLA抗体.     

Expression and function of B7-1 (CD80) and B7-2 (CD86) on human epidermal Langerhans cells

In addition to T cell receptor triggering, activation of T cells requires co-stimulatory signals that have been shown to be mainly initiated through CD28. We analyzed the expression and function of the two ligands for CD28, B7-1 (CD80) and B7-2 (CD86), on human Langerhans cells (LC), the antigen-presenting cells from epidermis. Human LC freshly isolated from epidermis (fLC) expressed significant level of B7-2, which was increased upon a short culture in vitro. In contrast, B7-1 was undetectable on fLC but appeared at the cell surface after a 3-day culture in vitro. Pre-incubation of 18-h cultured LC with anti-B7-2 monoclonal antibodies (mAb) was sufficient to abrogate the binding of CTLA4-Ig fusion protein, while a combination of both mAb against B7-1 and B7-2 was necessary to obtain a complete inhibition of CTLA4-Ig binding on 3-day cultured LC, showing the absence of a third CTLA4 ligand. The function of B7-1 and B7-2 on human LC has been analyzed by adding mAb at the beginning of mixed epidermal cell lymphocyte reactions. Anti-B7-2 mAb and CTLA4-Ig, but not anti-B7-1 mAb, strongly inhibited allogeneic, as well as recall antigen-induced T cell proliferation supported by fLC or 3-day cultured LC. Collectively, these results demonstrate that B7-2 is the major ligand for CD28/CTLA4 at the LC surface and that it plays a crucial role in human LC co-stimulatory function with little, if any, dependence on B7-1 expression.     

Both CD28 ligands CD80 (B7-1) and CD86 (B7-2) activate phosphatidylinositol 3-kinase, and wortmannin reveals heterogeneity in the regulation of T cell IL-2 secretion

In this report, the co-stimulatory signals provided by CD80(B7-1) or CD86 (B7-2) were compared to CD28 ligation by mAb.We demonstrate that while both anti-CD3 and anti-CD28 antibodiesinduced activation of phospholnositide (PI) 3-kinase, the kineticsof activation differed. Anti-CD28 produced a sustained activationof PI 3-kinase while anti-CD3 induced activation was transient.Both B7-1 and B7-2 could induce prolonged activation of PI 3-kinase.The co-stimulatory effects of B7-1 and B7-2 were dependent onCD28 cross-linking, based on complete inhibition of PI 3-kinaseactivation by CD28 antibody Fab fragments. While Jurkat T cellsco-stimulated with anti-CD3 and B7-1 or B7-2 secreted high levelsof IL-2, there were distinct effects of anti-CD28 mAb and B7-1or B7-2 on IL-2 secretion in conjunction with protein kinaseC activation. To assess functional effects of CD28 ligation,pharmacologic inhibitors of PI 3-kinase were evaluated. In Jurkatcells, efficient inhibition of PI 3-kinase activation afterB7-2 stimulation was achieved using wortmannin; however, weobserved a surprising increase in IL-2 secretion after B7 oranti-CD28 stimulation. The effect of wortmannin was concentrationdependent. Moreover, the effect was specific for receptor-mediatedactivation as wortmannin did not enhance phorbol ester pluslonomycin-induced IL-2 secretion. Another inhibitor of PI 3-kinase,LY294002, also resulted in augmentation of anti-CD28-inducedIL-2 secretion by Jurkat cells. The effects of wortmannin onIL-2 secretion were also examined in primary T cells. In markedcontrast, wortmannin resulted in a potent inhibition of anti-CD3plus B7-1 or anti-CD28-induced IL-2 secretion while phorbolester plus lonomycin-induced IL-2 secretion was wortmannin resistant.Together these observations demonstrate that signal transductionby both B7-1 and B7-2 involves PI 3-kinase, and that PI 3-kinaseor other wortmannin-sensitive targets are important for IL-2secretion. Finally, treatment of Jurkat cells with PI 3-kinaseinhibitors alone was sufficient to induce low levels of IL-2secretion. This is consistent with the notion that a wortmannin-sensitivetarget such as PI 3-kinase may down-regulate IL-2 secretionin Jurkat cells.     

B7-1分子诱导体外抗肝癌免疫反应

目的：了解Ｂ７分子在体外抗肝癌免疫中的作用。方法：健康人外周血单个核细胞（ＰＢＭＣ）与ＨｅｐＧ２／ｈＢ７－１，ＨｅｐＧ２／ｎｅｏ及亲代ＨｅｐＧ２瘤苗混合培养（ＭＬＴＣ），检测淋巴细胞活化增殖能力，淋巴细胞ＨＬＡ－Ｉ类抗原的表达，培养上清ＩＦＮ－γ水平，ＴＮＦ活性及ＬＡＫ，ＣＴＬ细胞活性。结果：ＨｅｐＧ２／ｈＢ７－１瘤苗促淋巴细胞增殖最高达１４．６倍，明显高于ＨｅｐＧ２／ｎｅｏ和ＨｅｐＧ２瘤苗的作用     

Expression and function of B7-1 and B7-2 in hapten-induced contact sensitivity

We analyzed the expression and function of the co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86) during contact sensitivity reactions induced by the hapten 2,4-dinitrofluorobenzene (DNFB). In the normal skin, only a few epidermal Langerhans cells or dermal dendritic cells express B7-2. In contrast, following challenge with DNFB, expression of B7-2 is up-regulated in both epidermis and dermis. Importantly, B7-1 is induced later and at lower levels compared to B7-2. Intravenous injections of anti-B7-2 mAb, but not anti-B7-1 mAb partially inhibit the hapten-induced contact sensitivity reaction. Experiments in which mice are injected differentially with anti-B7-2 mAb, either before the afferent or before the efferent phase of the contact sensitivity response, suggest that B7-2 is important for successful antigen priming.     

Distinct roles for B7 costimulation in contact hypersensitivity and humoral immune responses to epicutaneous antigen

Productive interactions between B7-1 and B7-2 costimulatory molecules on dendritic cells (DC) and CD28 on T cells are thought to be critical for successful antigen presentation. Epicutaneous application of haptens induces both contact hypersensitivity (CHS), an inflammatory cutaneous response mediated by CD8⁺ T cells, and an anti-hapten antibody response mediated by CD4⁺ helper T cells. The role of B7 costimulation in the immune response to oxazolone (Ox) was analyzed using mice lacking either B7-1 (B7-1 − / −), B7-2 (B7-2 − / −), or both (Db − / −) of these costimulatory molecules. The absence of both B7-1 and B7-2 results in diminished CHS. This inhibition is largely overcome at higher hapten sensitizing doses indicating the presence of compensatory pathways. In contrast, anti-Ox IgG1 and IgG2a responses were not detected in the absence of both B7-1 and B7-2, even at high sensitizing doses, indicating an obligatory role of B7 costimulation in IgG class switching. B7-1 and B7-2 have overlapping functions in both CHS responses and anti-hapten response. B7-2 − / − mice demonstrated a modestly reduced CHS response only at very low doses of Ox (0.05 %), but responded normally at higher Ox doses, and B7-1 − / − mice had CHS responses indistinguishable from those of wild-type mice. Similarly, anti-Ox IgG responses were comparable in wild-type, B7-1 − / − and B7-2 − / − mice. Taken together, these studies reveal distinct roles for B7 costimulation in response to epicutaneous antigens with an obligatory role for IgG class switching and an important, but nonessential role for CHS responses.     

In situ expression of B7 and CD40 costimulatory molecules by normal human lung macrophages and epithelioid cells in tuberculoid granulomas.

Normal alveolar macrophages (AM) are not efficient in inducing the proliferation of resting T lymphocytes, and, rather, tend to inhibit pulmonary immune responses. In contrast, epithelioid cells (EC), activated macrophages that play an essential role in the course of granulomatous responses, appear to stimulate T cell proliferation efficiently. The inability of macrophages to deliver potent costimulatory signals through the B7/CD28 and CD40/CD40L pathways could explain their weak accessory cell activity. Using MoAbs and immunohistochemical techniques, however, we found that essentially all AM in normal human lung tissue expressed B7-1, B7-2 and CD40 molecules, and most of these cells were strongly positive. Pulmonary macrophages in other compartments also expressed these costimulatory molecules; no differences in expression were observed comparing macrophages from smokers and non-smokers. Most AM recovered by bronchoalveolar lavage from normal lung segments also strongly expressed B7-1, B7-2 and CD40 molecules. In comparison, resting blood monocytes were B7-1- and only moderately positive for B7-2. Activation of monocytes with lipopolysaccharide (LPS) induced expression of these costimulatory molecules to levels similar to that of AM from the control subjects. EC in granulomatous lesions also expressed easily detectable levels of B7-1, B7-2 and CD40. T lymphocytes within and surrounding the granulomas expressed CD28, the counter-receptor for B7, and many of these T cells also expressed B7-1 and B7-2. These findings suggest that both AM and EC can deliver costimulatory signals through B7-1, B7-2 and CD40 molecules, and indicate that the impairment in accessory cell activity observed for normal AM cannot be attributed to the absence of expression of these costimulatory molecules.     

人B7-2(CD86) IgV+C段高效原核表达及活性测定

目的克隆、表达B7-2(IgV+C)并进行体外功能测定.方法用聚合酶链反应(PCR)技术从B7-2 cDNA中克隆B7-2(IgV+C),在此基础上构建表达B7-2(IgV+C)的原核表达载体pGEX-4T-3/hB7-2(IgV+C);SDS-PAGE检测蛋白表达,蛋白经变性、复性后在体外协同抗CD3单抗刺激人T细胞,3H-TdR掺入法检测T细胞的活化程度.结果在原核表达载体中成功地克隆了B7-2(IgV+C),SDS-PAGE表明在相对分子质量(Mr)55×103处有hB7-2(IgV+C)/GST融合蛋白的高效表达,其表达量占菌体总蛋白的33%.体外实验证明,此融合蛋白可协同抗CD3单抗刺激人T细胞活化.结论重组蛋白B7-2(IgV+C)在第一信号存在下可活化T细胞,即具有共刺激活性.     

Compartmentalization of T cell responses following respiratory infection with Bordetella pertussis: hyporesponsiveness of lung T cells is associated with modulated expression of the co-stimulatory molecule CD28

We have used a murine respiratory challenge model to examine the local T cell responses in the lung during infection with Bordetella pertussis. T cells from lung parenchyma and airways of naive and infected mice were refractory to both antigen and mitogen stimulation in the presence of lung macrophages. Furthermore irradiated mononuclear cells from the lungs suppressed antigen and mitogen-induced proliferation, but not IFN-γ production, by splenic T cells. Removal of macrophages and stimulation of purified lung T cells in the presence of irradiated splenic antigen-presenting cells fully restored the response to mitogen. However, T cells purified from the lung during the acute phase of infection with B. pertussisfailed to proliferate or produce detectable levels of IL-2, IL-4, IL-5 or IFN-γ in response to purified bacterial antigens. In contrast, splenic T cells from these animals produced high levels of IL- 2 and IFN-γ and proliferated strongly to a range of bacterial components. Phenotypic analy sis of bronchoalveolar lavage cells during the course of infection revealed transient infiltra tion of neutrophils, followed by macrophages, CD4+ T cells and smaller numbers of CD8+ T cells and γ δ+ T cells. Cell surface expression of B7 on infiltrating macrophages and CTLA-4 on T cells did not change significantly during infection. However, expression of the CD28 co- stimulatory molecule was profoundly reduced on lung T cells during the acute phase of infection. In contrast, lung T cells from mice primed by B. pertussisinfection or vaccination were resistant to CD28 down-regulation. These results suggest compartmentalization of T cell responses between the lung and the periphery during B. pertussisinfection and that B. pertussismay have immunomodulatory properties on local T cell populations in the lungs of naive mice.     

Potential role of B7-1 and CD28 molecules in immunosuppression in leprosy

In order to understand the mechanism of unresponsiveness towards Mycobacterium leprae antigens in leprosy, we evaluated the role of M. leprae sonicate antigens in regulating the expression of the costimulatory molecules B7-1, CD28, intercellular adhesion molecule-1 (ICAM-1), LFA-1α, LFA-1β and Mac-1 on the lymphocytes of both leprosy patients and healthy subjects. It was observed that the expression of B7-1 and CD28 was significantly decreased but the levels of ICAM-1 and LFA-1α were increased in patients with untreated borderline leprosy (BL)/lepromatous leprosy (LL) disease. No remarkable change was noticed in the case of borderline tuberculoid (BT) leprosy or treated BL/LL patients. Further, a striking finding was that lymphocytes from healthy subjects cultured with a particularly high dose of M. leprae sonicate antigens down-regulated the expression of B7-1 and CD28 molecules, but up-regulated the display of ICAM-1 and LFA-1α. Furthermore, proliferation induced by M. leprae sonicate was inhibited only by anti-B7-1 antibody. Mycobacterium leprae antigen-induced suppression of the proliferation of lymphocytes of healthy volunteers and LL patients was reversed by culturing the lymphocytes with purified protein derivative (PPD). It may be concluded from the findings in this study that down regulation of B7-1 and CD28 in BL/LL leprosy patients may be responsible for a defective T cell signalling by the B7-1/CD28 pathway caused by M. leprae antigens. This may lead to clonal inactivation of M. leprae-reactive T cells, consequently the bacilli grow without restriction in macrophages.