Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Mechanistic insight of interleukin-9 induced osteoclastogenesis

Interleukin (IL)-9 is an emerging player in the pathogenesis of various chronic inflammatory diseases including bone disorders like rheumatoid arthritis (RA) and psoriatic arthritis. Recently, IL-9 was shown to enhance the osteoclast formation and their function in RA. However, the mechanisms by which IL-9 influences osteoclastogenesis are not known. Therefore, in this study we aimed to unravel the direct and indirect ways by which IL-9 can influence osteoclast formation. We used mouse bone marrow precursor cells for checking the effect of IL-9 on osteoclast differentiation and its function. Next, IL-9 induced signalling pathway were checked in the process of osteoclastogenesis. T cells play an important role in enhancing osteoclastogenesis in inflammatory conditions. We used splenic T cells to understand the impact of IL-9 on the functions of T effector (Teff) and regulatory T (Treg) cells. Furthermore, the effect of IL-9 mediated modulation of the T cell response on osteoclasts was checked using a coculture model of T cells with osteoclast precursors. We showed that IL-9 enhanced osteoclast formation and its function. We found that IL-9 activates STAT3, P38 MAPK, ERK1/2, NFκB and we hypothesize that it mediates the effect on osteoclastogenesis by accelerating mitochondrial biogenesis. Additionally, IL-9 was observed to facilitate the functions of pro-osteoclastogenic IL-17 producing T cells, but inhibits the function of anti-osteoclastogenic Treg cells. Our observations suggest that IL-9 can influence osteoclastogenesis directly by modulating the signalling cascade in the precursor cells; indirectly by enhancing IL-17 producing T cells and by reducing the functions of Treg cells.     

Decreased frequency of a novel T-lymphocyte subset,CD3+CD4−CD7+CD57− T cells,in hepatitis B virus-related end-stage liver disease might contribute to disease progression

CD7 and CD57 are related to the differentiation and functional stages of CD8⁺ T cells. However, the role of their combined presence in CD8⁺ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3⁺CD4⁻CD7⁺CD57⁻ T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3⁺CD4⁻CD7⁺CD57⁻ T cell frequency. Furthermore, the prevalence of CD3⁺CD4⁻CD7⁺CD57⁻ T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3⁺CD4⁻CD7⁺CD57⁻ T cells in a dose-dependent manner. CD3⁺CD4⁻CD7⁺CD57⁻ T cells displayed a B and T lymphocyte attenuator (BTLA)^highCD25^highCD127^high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.     

烧伤患者外周血T淋巴细胞亚群变化动态观察

为探讨烧伤后机体细胞免疫紊乱的机制,动态观察了30例不同烧伤面积患者不同时间的T淋巴细胞亚群变化情况.结果发现:中度烧伤组CD3,CD8伤后变化不大,CD4及CD4/CD8比值至伤后第二周起明显低于正常对照组:重度烧伤组,伤后一周CD3,CD4及CD4/CD8比值即明显降低,至伤后三周CD8明显高于对照组,特重烧伤组,伤后一周即出现CD3,CD4及CD4/CD8比值明显降低,而CD8则明显升高.结论:(1)烧伤后T淋巴细胞亚群的改变是烧伤患者免疫功能低下的原因之一;(2)中度烧伤患者CD/CD8比值下降,主要是由CD4下降所致而重度及特重度烧伤患者CD4/CD8比值下降则是由CD4下降和CD8上升共同作用所致;(3)烧伤面积越大,细胞免疫功能下降越明显,其发生机理越复杂.     

CD3AK细胞对烧伤患者免疫功能的影响

通过检测患者淋巴细胞转化功能及NK细胞活性,调查CD3AK细胞对烧伤患者免疫功能的影响.结果发现:CD3AK细胞使T细胞转化为母细胞能力增加,NK细胞活性升高,表明CD3AK细胞能改善烧伤患者免疫功能低下的状态,促进细胞免疫功能的恢复.     

肿瘤抗原MAGE-3预测CTL表位的合成与鉴定

目的 合成并鉴定已预测出的４个ＭＡＧＥ－３ ＨＬＡ－Ａ２限制性ＣＴＬ表位多肽,为后续研究奠定基础。方法 采用固相合成法合成多肽,经ＲＰ－ＨＰＬＣ纯化、纯度分析,用质谱进行定性鉴定。结果 ４个合成肽的纯度都在９５％以上,经质谱分析,各肽的分子量测定值与理论值相符,结论 所得多肽为高纯度的目标肽,为后续研究提供了可靠的保证。     

急性T淋巴细胞白血病细胞系JM分泌抑制因子在体外对T细胞凋亡及细胞周期的影响

目的　研究急性 T淋巴细胞白血病细胞系 JM分泌的抑制因子 (TL SFJM)在体外对 T细胞凋亡及细胞周期的影响 .方法　以 TL SFJM作用于有丝分裂原 PHA、蛋白激酶 C(PKC)活化剂 PMA和同种异体抗原 (alloantigen)活化的人或小鼠 T细胞 ,应用流式细胞仪检测细胞凋亡及细胞周期 .结果　 TL SFJM在体外可诱导 PHA/IL - 2活化的小鼠胸腺细胞的凋亡 .TL SFJM在体外可诱导 alloantigen活化的人外周血单个核细胞 (PBMC)的凋亡 ,且把细胞周期阻遏在 G1期 .TL SFJM对 PMA诱导的人 PBMC活化抗原 CD2 5的表达无明显影响 ,也不引起凋亡 .结论　 TL SFJM在体外可诱导 PHA、alloantigen活化的 T细胞凋亡 .     

糖尿病患者T细胞亚群、甲状腺功能与中医辨证的关系

了解Ｔ淋巴细胞亚群及甲状腺功能与糖尿病中医辨证的关系。方法将４１例糖尿病患分为气阴两虚型和阴阳两虚型两组,采用间接免疫荧光法和放射免疫法分别测定Ｔ淋巴细胞亚群及甲状腺功能。结果气阴两虚型ＣＤ＾４＋,ＣＤ＾＋８及ＣＤ＾４＋８／ＣＤ＾＋无变化,Ｔ３,Ｔ３／ｒＴ３降低;阴阳两虚型ＣＤ＾＋８值升高,ＣＤ＾＋４／ＣＤ＾＋８值降低,Ｔ３,Ｔ４,ＦＴ３,ＦＴ４,Ｔ３／Ｒｔ３值降低,ｒＴ３升高。与正常对照组均有     

急性缺血性心肌损伤患者肌钙蛋白T检测的临床意义

目的 :为了早期、准确地判定急性缺血性心肌损伤程度。方法 :采用酶联免疫吸附方法 ,对 41例急性心肌梗塞患者、 38例心绞痛 (AP)疑有微小心肌损伤 (MMD)患者以及 40例健康 (HP)人进行心脏肌钙蛋白 T(c Tn T)测定 ,同时与 CK和CK— MB两项酶学指标相比较。结果 :AMI组 ,c Tn T、CK及 CK— MB三者之间的异常率无明显差别 (异常率 97%～ 10 0 % ) ;而AP组 ,c Tn T的异常率为 44 .7% ,明显高于 CK异常率的 7.9%和 CK— MB异常率的 13.2 %。与健康组相比 ,AP组的 c Tn T测定的水平明显高于对照组水平 (P<0 .0 1)。结论 :对于不同程度的急性缺血性心肌损伤的诊断 ,c Tn T较 CK及 CK— MB,具有更高的灵敏度及特异性。     

EFFECTS OF MICROWAVE TREATMENT ON THE LYMPHOCYTESUBSETS IN CASES OF CHRONIC LYMPHEDEMA OF EXTREMITIES

R68llm6 Objectif Pour determiner l'dtat immunitaire des sons-groups l~taires T des malades aveclwtoeddlne chronique des extremitys et l' effet du traitement per micrreondes. ANt~ ie malades avec Iy7nphedimedes extradites(n = 20 ) et ies volontaires no~ux (n = 10 ) out ate studies per FITC on PHmerque MOAbs et cytometrie dcouleur double pour erminer ies changements des Phenotype l~taires T chez ies malades avec lpephoeddnZe aunt et aprdstraitement. ~flats Le rdsultat a montrd que ie pourc…