HIV/HCV共感染者抗逆转录病毒治疗后免疫恢复情况

由于具有相同的传播途径,人类免疫缺陷病毒(Human immunodeficiency virus,HIV)和丙型肝炎病毒(Hepatitis C virus,HCV)共感染非常普遍,但是关于合并感染的程度,两种病毒之间的相互关系,在艾滋病抗逆转录病毒治疗(Antiretroviral therapy,ART)前后,HCV合并感染对HIV患者免疫细胞恢复的影响仍不明确。为了通过分析CD4⁺和CD8⁺T淋巴细胞数的变化,以了解辽宁省HIV/HCV共感染者ART后免疫恢复的情况,本研究从辽宁省艾滋病抗病毒治疗数据库中筛选符合要求的HIV感染者和HIV/HCV共感染者,收集感染者基本人口学资料及HCV抗体检测结果、HIV/HCV共感染途径等资料。采用t检验或卡方检验进行组间比较,采用Kaplan-Meier乘积极限法绘制生存分析函数图。结果显示,本研究共纳入HIV感染者12742人,HIV/HCV共感染者340人。HIV感染者和HIV/HCV共感染者的不同人口学特征均差异显著(P<0.001)。HIV感染和HIV/HCV共感染者ART治疗后CD4⁺细胞数和CD4⁺/CD8⁺比值显著升高(P<0.05),CD8⁺细胞数比ART前显著下降(P<0.05)。HIV/HCV共感染者随着ART时长,CD4⁺T淋巴细胞数恢复情况始终显著低于HIV感染者(P<0.05)。生存分析曲线表明,HCV/HIV共感染者从艾滋病诊断开始随着ART的治疗CD4⁺细胞恢复情况显著低于HIV感染者,Log-Rank检验统计量为4.483(P=0.034)。本研究揭示,HCV感染对ART患者CD4⁺和CD8⁺T淋巴细胞的恢复有影响。ART后HIV/HCV共感染者中CD4⁺T淋巴细胞计数的改善低于HIV单一感染者,并且单一感染患者对ART的反应比合并感染患者更好。因此,建议在启动ART之前,对每个感染HIV的患者进行HCV抗体筛查。     

受体相互作用蛋白激酶-3参与甲型H1N1流感病毒感染小鼠记忆性CD8＋ T细胞的应答

受体相互作用蛋白激酶-3(receptor-interacting protein kinase 3, RIPK3)是坏死复合体的关键成分之一,介导细胞程序性死亡(programmed cell death,PCD)的发生。前期研究发现流感抗原特异性CD8^＋T细胞的初次应答部分依赖于RIPK3分子,为探讨其在记忆性CD8^＋T细胞应答中的作用,对初次感染后的C57BL/6小鼠在免疫记忆阶段进行了再次感染,并用流式细胞仪检测了流感病毒特异性的记忆性CD8^＋T细胞的表型和功能。结果发现小鼠初次感染甲型 H1N1流感病毒株A/Puerto Rico/8/34后37 d, RIPK3敲除小鼠的CD8^＋T细胞比例及分泌细胞因子γ-干扰素(IFN-γ)和肿瘤坏死因子-α(TNF-α)的能力均显著低于野生型小鼠;在再次感染相同病毒时,RIPK3敲除小鼠流感病毒特异性CD8^＋T细胞比例及分泌细胞因子IFN-γ的能力依旧显著低于野生型小鼠;而CD8^＋中枢型记忆性T细胞(TCM)比例显著高于野生型小鼠,效应型记忆性T细胞(TEM)或效应性T细胞(TEff)比例却显著低于野生型小鼠。提示RIPK3分子参与调节流感病毒特异的记忆性CD8^＋T细胞诱生数量和分泌细胞因子功能,并影响其TCM与TEM/TEff的比例,为深入探索病毒特异的记忆性CD8^＋T细胞应答的分子机制提供了新线索。     

α1-肾上腺素受体对胶原诱导性关节炎小鼠Treg细胞功能的影响*

目的: 利用胶原诱导性关节炎 (CIA) 模型小鼠,探讨去甲肾上腺素 (NE) 及其α1-肾上腺素受体 (AR ) 对CIA小鼠Treg细胞的作用。方法: 雄性DBA/1小鼠 32 只,随机分为对照组 (n=8) 和CIA模型组 (n=24)。II型胶原 (CII) 乳剂100 μl 尾根部注射DBA/1小鼠制备CIA小鼠模型,在初次免疫后第 41 日,用免疫荧光法检测小鼠脾脏中CD4⁺T与α1-AR的共定位情况;用Western blot法检测小鼠踝关节和脾脏中α1-AR的蛋白表达。分离纯化CIA小鼠脾脏中CD4⁺ T细胞,用抗CD3和抗CD28的单克隆抗体刺激CD4⁺T细胞,进行细胞培养,分为未加药组和加药组,加药组用NE或α1-AR激动剂苯肾上腺素 (phenylephrine) 处理细胞,用流式细胞术检测CIA小鼠CD4⁺T细胞中Treg的细胞数;用Western blot法检测CIA小鼠CD4⁺T中转化生长因子-β (TGF-β) 和IL-10的蛋白表达。结果: CD4⁺ T细胞能够表达α1-AR;与对照组相比,CIA小鼠踝关节和脾脏中α1-AR的蛋白表达显著降低(P＜0.01);与未加药的CIA小鼠的CD4⁺ T细胞相比,NE加入后的CIA小鼠CD4⁺ T细胞中Treg细胞的功能显著增强(P＜0.01);α1-AR激动剂phenylephrine加入后的CIA小鼠CD4⁺ T细胞中Treg细胞的功能显著增强(P＜ 0.01)。结论: 激活CIA小鼠CD4⁺ T细胞上的α1-AR可增强Treg细胞的功能,促进CD4⁺ T细胞向Treg细胞方向分化,发挥抗炎作用。     

老年呼吸机相关性肺炎患者肠道菌群特征及其与疾病的相关性

目的 探讨老年呼吸机相关性肺炎(VAP)患者肠道菌群特征及其与疾病的相关性,为该类患者的治疗提供参考。方法 选择2018年1月至2020年1月在该院进行机械通气的患者141例,根据是否发生VAP分为VAP组(n=67)和非VAP组(n=74),同时选择同期在我院进行体检的健康者为对照组(n=50)。采用16S rRNA荧光定量PCR法检测3组研究对象肠道双歧杆菌和大肠埃希菌数量,并计算B/E值。采用流式细胞仪检测T淋巴细胞亚群CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺、CD4⁺/CD25⁺、CD8⁺/CD28^-以及CD8⁺/CD28⁺细胞水平。采用改良酶学分光光度法检测血浆D-乳酸水平。采用Pearson相关检验分析VAP组B/E值与免疫功能及血浆D-乳酸的相关性。结果 VAP组患者肠道双歧杆菌数量、B/E值显著低于非VAP组和对照组,大肠埃希菌...     

非人类免疫缺陷病毒感染马尔尼菲青霉病9例临床特征分析及文献复习

为探讨和总结非人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者发生马尔尼菲青霉病的临床特点,回顾性研究复旦大学附属华山医院感染科2007年1月-2017年8月收治的9例及同期发表文献中的马尔尼菲青霉病病例,分析其临床表现、实验室检查、治疗及转归。9例马尔尼菲青霉病患者的HIV检测均为阴性,5例CD4^＋ T细胞计数正常。非HIV感染马尔尼菲青霉病的起病较缓,临床表现与经典马尔尼菲青霉病类似,真菌血症较少见,病理特点以肉芽肿改变及化脓性炎症为主,诊断方法仍以培养为主(8/9),1例通过病理及二代测序技术诊断。目前,非HIV感染马尔尼菲青霉病发病率有升高趋势,部分发生于免疫正常人群,需引起临床医师的重视。     

BALB/c小鼠作为单纯疱疹病毒1型感染模型的免疫学分析

在单纯疱疹病毒1型(herpes simplex virus type 1,HSV-1)小鼠感染及其相关研究中,临床病理和免疫学指标对其分析具有重要技术意义。本研究观察了HSV-1在不同条件下感染BALB/c小鼠后的多个免疫学指标,包括外周血单核细胞(peripheral blood mononuclear cell,PBMC)群体中树突细胞比例及功能、血清中和抗体水平、PBMC中HSV-1抗原特异性T细胞水平,以及潜伏感染期小鼠神经组织中CD8^＋ T细胞浸润情况。结果显示,HSV-1毒株Mckrae、17＋以角膜及滴鼻途径感染3周龄及6周龄BALB/c小鼠后,小鼠PBMC中树突细胞数量增加,并显示出刺激病毒抗原特异性T细胞增殖的能力。病毒感染后35 d,小鼠PBMC中未检测到白细胞介素4(interleukin 4,IL-4)^＋抗原特异性T细胞,但能检测到低水平的γ干扰素(interferon γ,IFN-γ)^＋抗原特异性T细胞;小鼠血清中未检测到或仅能检测到低水平的中和抗体。HSV-1以皮下及足垫注射途径感染BALB/c小鼠90 d后,足垫感染途径较皮下感染诱导出更高水平的血清中和抗体,PBMC中可检测到IL-4^＋及IFN-γ^＋抗原特异性T细胞,但不同毒株及小鼠周龄之间出现T细胞反应程度差异。组织病理学结果表明,各组小鼠三叉神经组织中均有CD8^＋ T细胞浸润。这些结果提示,不同HSV-1毒株以不同途径感染不同周龄BALB/c小鼠后,均可刺激树突细胞成熟及呈递病毒抗原,但血清中和抗体及PBMC中病毒抗原特异性T细胞水平在不同毒株、感染途径及小鼠周龄之间有差异。     

艾滋病免疫重建治疗策略的研究进展

获得性免疫缺陷综合征( AIDS) 是由人类免疫缺陷病毒( HIV) 侵犯并破坏机体免疫系统引起的疾病。20 世纪90 年代前, 人们普遍认为免疫系统的破坏是不可逆转的, 但自高效抗反转录病毒疗法出现以后, 发现受损的免疫功能可以获得重建并成为研究的热点。免疫功能重建是指患者受损的免疫功能恢复到正常水平或接近正常水平, 从而降低机会性感染和肿瘤的发生, 降低发病率和病死率。随着各项技术的发展和改进, AIDS 的发病机制和免疫重建机制得到进一步研究, 改善调节患者CD4⁺细胞的数量和免疫功能及细胞毒性T细胞( CTL) 的杀伤功能是最重要的保护性免疫机制。目前一些治疗新策略和手段, 如细胞因子治疗、HIV 特异性疫苗的研制已进入试验或临床阶段, 以期进一步改善患者的免疫功能。     

肠上皮细胞Tlr4特异性敲除基因鼠鉴定及免疫学特征观察

目的 鉴定肠上皮Tlr4特异性敲除(Tlr4^f/f cre T)鼠,评价其免疫学特征。方法 应用CRISPR/Cas9技术构建Tlr4^f/f cre T基因鼠,PCR和免疫荧光鉴定Tlr4^f/f cre T基因鼠基因型,观察基因鼠的一般生物学特征、繁殖能力和子代存活率。HE染色、流式细胞术及ELISA比较基因鼠和野生型小鼠免疫器官结构、肠黏膜免疫细胞比例及细胞因子分泌水平差异。结果 从基因和蛋白水平验证Tlr4^f/fcre T基因鼠的建立。与野生型鼠比,Tlr4^f/f cre T基因鼠的一般生物学特征无明显差异、子代存活率> 90%;胸腺、脾及肝生理结构无显著性差异;脾淋巴细胞增殖能力、血清及肠黏膜细胞因子分泌水平无显著性差异;但CD4⁺T和γδT细胞显著减少。结论 成功构建了肠上皮Tlr4特异性敲除小鼠(Tlr4^f/f cre T),为研究肠上皮Tlr4基因在肠道疾病、肿瘤及代谢性疾病中的作用提供实验手段。     

肿瘤干细胞与胃癌

最近的一项研究报导,采用流式细胞仪分选技术从人胃癌细胞株中分离出CD44^＋胃癌干细胞. 20～30×10³个CD44＋细胞入NOD/SCID 鼠腹部皮下和胃浆膜下能形成胃癌移植瘤, 100×10³个CD44^－的细胞入NOD/SCID 鼠体内不形成肿瘤.采用无血清、无粘附间质的干细胞体外培养方法,发现CD44^＋的细胞能形成肿瘤微球体,具有自我更新能力,而CD44^－的细胞则不形成球形克隆.上述的实验结果说明,在人胃癌细胞株中存在胃癌肿瘤干细胞.据此可以相信,胃癌干细胞是胃癌细胞中具有自我更新及分化潜能的一小群细胞,不能被目前的化疗、放疗等抗癌治疗措施所杀灭,是胃癌术后复发、肿瘤进展扩散转移的根源.胃癌干细胞可能来源于骨髓干细胞.随着对胃癌肿瘤干细胞生物学研究的深入,必将为胃癌的临床诊断和治疗提供新的策略.     

重庆地区人类免疫缺陷病毒携带者的微孢子虫感染情况调查

目前我国关于微孢子虫感染人的研究相对较少,更没有关于重庆地区人类免疫缺陷病毒(HIV)携带者感染微孢子虫的数据统计。对重庆市公共卫生医疗救治中心收治的22例HIV抗体阳性,但尚未接受抗病毒治疗的患者进行研究。将22例患者粪便样本分别提取总DNA,通过聚合酶链反应(PCR)法和DNA测序等技术对微孢子虫在患者中的感染情况进行检测,并对微孢子虫种类进行鉴定。同时对22例患者的免疫细胞亚群进行计数和分析。结果显示,微孢子虫的感染率为36.3%(8/22),主要由脑炎微孢子虫属(Encephalitozoon spp)的海伦脑炎微孢子虫(E. hellem)和肠脑炎微孢子虫(E. intestinalis)引起。22例患者的免疫细胞亚群分析显示,平均淋巴细胞数0.93±0.13×10⁹/L,CD4^＋T细胞数132±22 个/mL,CD8^＋T细胞数495±91 个/mL,CD4/CD8细胞比值0.37±0.1,表明患者免疫功能受到严重抑制。进一步将微孢子虫感染患者与未感染患者的免疫细胞亚群进行比较发现,感染患者淋巴细胞数为0.51±0.1×10⁹/L,未感染患者为1.17±0.17 ×10⁹/L,两者具有显著差异(P<0.05);感染患者CD4^＋T细胞数为71±27 个/mL,未感染患者为167±28 个/mL,两者具有显著差异(P<0.05);感染患者CD8^＋T细胞数为209±35 个/mL,未感染患者为658±123 个/mL,两者具有显著差异(P<0.05),以上表明微孢子虫感染组的免疫功能受损情况更严重。本研究结果提示微孢子虫的机会性感染与患者免疫功能受损情况密切相关,脑炎微孢子虫属在重庆地区有较高的感染率,这为进一步阐明微孢子虫与宿主相互作用关系奠定基础,也为公共卫生健康管理提供重要参考。     

Selective expansion and enhanced anti-tumor effect of antigen-specific CD4+ T cells by retrovirus-mediated IL-15 expression

Mounting evidence has demonstrated that CD4⁺ T cells play an important role in anti-tumor immune responses. Thus, adoptive transfer of these cells may have great potential for anti-cancer therapy. However, due to the difficulty to generate sufficient tumor-specific CD4⁺ T cells, the use of CD4⁺ T cells in tumor therapy is limited. It has been found that IL-15 transfection enhances the proliferation and anti-tumor activity of tumor-specific CD8⁺ T cells, but the effect of IL-15 transfection on CD4⁺ T cells remains unknown. Here, the effects of retrovirus-mediated IL-15 expression in Ova-specific CD4⁺ T cells from Do11.10 mice were evaluated and it was discovered that IL-15 transfected CD4⁺ T cells expressed both soluble and membrane-bound IL-15. Retrovirus-mediated IL-15 expression led to a selective expansion of antigen-specific CD4⁺ T cells by inhibiting their apoptosis. Invivo IL-15 transfected CD4⁺ T cells were more effective in suppressing tumor growth than control retroviral vector transfected ones. To ensure the safety of the method, the employment of thymidine kinase gene made it possible to eliminate these transgenic CD4⁺ T cells following ganciclovir treatment. Together, we show that IL-15 transfection induced a selective expansion of antigen-specific CD4⁺ T cells ex vivo and enhanced their tumor-suppression effects in vivo. This has an important significance for improving the efficacy of adoptive T cell therapy.     

广西人类免疫缺陷病毒感染者/艾滋病患者合并马尔尼菲篮状菌感染的特征及Mp1p抗原快速筛检的研究

为调查广西人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者/艾滋病(acquired immunodeficiency syndrome,AIDS)患者合并马尔尼菲篮状菌(Talaromyces marneffei,TM)感染的特征并评价TM Mp1p(一种甘露糖蛋白)抗原试剂...     

Poor Immune Reconstitution in HIV-Infected Patients Associates with High Percentage of Regulatory CD4+ T Cells

CD4⁺ regulatory T cells (Tregs) are essential for the maintenance of the immune system''s equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4⁺ T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4⁺ T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4⁺ T cell counts achieved) <200 cells/µL, the individuals with high Tregs percentages (≥10% of total CD4⁺ T cells) had the worse CD4⁺ T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4⁺ T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4⁺ T cell recovery among immunological non-responder HIV⁺ individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4⁺ T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation.     

Effect of Baseline HIV Disease Parameters on CD4+ T Cell Recovery After Antiretroviral Therapy Initiation in Kenyan Women

Background

Antiretroviral therapy (ART) for HIV infection reconstitutes the immune system and improves survival. However, the rate and extent of CD4+ T cell recovery varies widely. We assessed the impact of several factors on immune reconstitution in a large Kenyan cohort.

Methodology/Principal Findings

HIV-infected female sex workers from a longitudinal cohort, with at least 1 year of pre-ART and 6 months of post-ART follow-up (n = 79), were enrolled in the current study. The median pre-ART follow-up was 4,040 days. CD4 counts were measured biannually and viral loads where available. The median CD4 count at ART initiation was 180 cells/ul, which increased to 339 cells/ul at the most recent study visit. The rate of CD4+ T cell increase on ART was 7.91 cells/month (mean = 13, range −25.92 to 169.4). LTNP status prior to ART initiation did not associate with the rate of CD4 recovery on ART. In univariate analyses, associations were observed for CD4 recovery rate and duration of pre-ART immunosuppression (r = −0.326, p = 0.004) and CD4 nadir (r = 0.284, p = 0.012). In multivariate analysis including age, CD4 nadir, duration of HIV infection, duration of pre-ART immunosuppression, and baseline viral load, only CD4 nadir (p = 0.007) and not duration of immunosupression (p = 0.87) remained significantly associated with the rate of CD4 recovery.

Conclusions/Significance

These data suggest that prior duration of immune suppression does not predict subsequent recovery once ART is initiated and confirm the previous observation that the degree of CD4 depletion prior to ART initiation is the most important determinant of subsequent immune reconstitution.     

骨髓间充质干细胞对肾移植受者T淋巴细胞分化和miRNA-155表达的影响

目的探讨骨髓间充质干细胞（MSCs）对肾移植受者T淋巴细胞分化和miRNA-155表达的影响。 方法选取2013年1月至2017年12月于福州总医院接受MSCs诱导+同种异体肾移植术的受者20例（MSCs组）,对照组为同期配对的异体肾移植受者20例。两组患者术后免疫抑制方案均为霉酚酸酯+他克莫司+强的松。两组患者分别于移植术前、术后第15天抽取静脉血,流式细胞仪检测外周血CD4⁺ CD25⁺ FoxP3⁺ Treg细胞/?CD4⁺细胞亚群比值;ELISA检测白细胞介素2（IL-2）、肿瘤坏死因子α（TNF-α）和白细胞介素10（IL-10）浓度;免疫磁珠分选外周血T淋巴细胞后,Rea1-time PCR法检测外周血T淋巴细胞中miRNA-?155的表达。两组间均数比较采用独立t检验,治疗前后均数比较采用配对t检验。 结果移植前两组肾移植受者外周血CD4⁺ CD25⁺ FoxP3⁺ Treg细胞/?CD4⁺细胞比值、IL-2、IL-?10、TNF-α、T淋巴细胞miRNA-155表达水平差异均无统计学意义（P均> 0.05）;术后第15天,与对照组相比,MSCs组外周血CD4⁺ CD25⁺ FoxP3⁺ Treg细胞/?CD4⁺细胞亚群比值（30.44﹪?± 4.23﹪? vs 26.06﹪?±4.77﹪,t = 2.365,P = 0.042）、IL-10水平（20.35?ng/?L?±?5.10?ng/?L? vs 16.63?ng/?L±6.26?ng/?L,t = 2.062,P?=?0.046）上升,而IL-2（27.47ng/?L±4.30 ng/?L vs 31.40?ng/?L±5.33 ng/L,t = 2.252,P = 0.015）、TNF-α（41.52?ng/?L±8.32?ng/L vs 46.67?ng/?L±6.71?ng/L,t = 2.157,P = 0.037）和T淋巴细胞miRNA-155表达水平（1.61±0.31 vs 1.89±0.15,t = 3.688,P?= 0.001）则降低。 结论MSCs能够升高肾移植受者外周血CD4⁺ CD25⁺ FoxP3⁺ Treg细胞/?CD4⁺细胞比值和IL-10水平,降低IL-2、TNF-α和T淋巴细胞miRNA-155表达水平,与MSCs的免疫耐受诱导有关。     

恶性血液病患者外周血淋巴细胞亚群变化及其临床意义的研究

目的: 探讨恶性血液病外周血淋巴细胞亚群变化特征及临床意义。方法: 采用流式细胞仪检测64例初诊的血液系统恶性肿瘤患者的外周血淋巴细胞亚群。病种包括急性髓系白血病(acute myeloid leukemia,AML)、急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)、霍奇金淋巴瘤(Hodgkin’s lymphoma,HL)、非霍奇金淋巴瘤(Non-Hodgkinlymphoma,NHL)。分析比较30例正常人的外周血淋巴细胞亚群与实验组的差异,并对64例恶性血液病患者中连续动态监测的21例急性白血病患者外周血淋巴细胞亚群结果变化与预后关系进行分析。结果： 不同成人恶性血液病患者年龄分组淋巴细胞亚群变化无明显差异;恶性血液病患者中CD3 ⁺CD8 ⁺ T淋巴细胞百分比、Treg细胞百分比均增加;CD16 ⁺/CD56 ⁺NK细胞百分比及CD4 ⁺/CD8 ⁺比值均下降;CD3 ⁺T淋巴细胞数量、CD3 ⁺CD4 ⁺淋巴细胞数、CD3 ⁺CD8 ⁺淋巴细胞数量、CD3 ^-CD19 ⁺淋巴细胞数量、CD16 ⁺/CD56 ⁺NK淋巴细胞数量及CD4 ⁺/CD8 ⁺比值均减少;急性白血病及恶性淋巴瘤患者外周血淋巴细胞亚群与正常对照组比较存在一定的差异;急性白血病未缓解组的Treg细胞比例明显高于急性白血病首疗程缓解组及对照组;急性白血病复发组Treg细胞比例明显高于急性白血病持续缓解组以及对照组;对21例急性白血病患者动态监测的淋巴细胞亚群发现,化疗缓解的患者Treg在化疗过程中逐渐下降,至第3~6个疗程逐渐接近正常对照,化疗未缓解的患者Treg细胞在化疗过程中逐渐上升或持续大于10%,明显高于完全缓解组,复发患者Treg在化疗过程中先下降后明显上升。 结论： 恶性血液病患者免疫功能显著低于健康人,且伴随免疫功能紊乱,且不同疾病类型、不同的疾病状态免疫紊乱的程度不一,Treg细胞比例可以用来预测急性白血病患者疗效及复发,可以为患者的临床治疗方案及用药强度提供指导依据。     

Anatomy of a pulmonary immune response: Kinetics in different leukocyte pools

In pulmonary immune reactions the cells which can be obtained by bronchoalveolar lavage (BAL) are only one part of the picture. In this study the kinetics of an experimental pulmonary immune response were investigated simultaneously in different lung compartments in the same rat. On days 0, 1, 2, 3, 4, 5 and 11 after intratracheal challenge with sheep red blood cells, leukocytes were taken from the bronchoalveolar, the interstitial and the marginal lung vascular pool as well as from the peripheral blood. Total numbers of granulocytes, NK cells, B and T cells, CD4⁺ and CD8⁺ cells were determined. Histology and in vivo labeling of proliferating cells was performed. On day 1 after challenge an increase of granulocytes in the BAL was found. In the BAL the total number of T lymphocytes increased on day 1 and day 2 and the CD4/CD8 ratio increased from day 1 to day 5, indicating an influx of CD4⁺ T cells. Changes in the lung interstitium showed a similar tendency, but were not found in the marginal pool or blood. Histologically cellular infiltrates were seen around the pulmonary small vessels. Little local proliferation occurred in the different lung compartments, indicating mainly immigration of cells. Further studies will focus on the expression of adhesion molecules during an immune response, to learn more about the mechanisms responsible for the increase of lymphocytes.