间充质干细胞对系统性红斑狼疮CD4+Foxp3+T淋巴细胞的调节

目的 探讨同种异体骨髓间充质干细胞(MSC)体内外对系统性红斑狼疮(SLE)患者外周血CD4+Foxp3+T淋巴细胞及人脐带MSC移植对MRL/lpr鼠脾脏和淋巴结CD4+Foxp3+T淋巴细胞水平的影响.方法 血缘相关供者骨髓中分离培养MSC移植治疗5例SLE患者,采用流式细胞术检测移植前后外周血CD4+Foxp3+T淋巴细胞百分率.7例SLE患者外周血单个核细胞(PBMC)分别与SLE患者和正常人骨髓MSC按不同比例体外共培养72 h,检测共培养后PBMC中CD4+Foxp3+T淋巴细胞百分率.MRL/Ipr鼠输注脐带MSC后检测脾脏和淋巴结CD4+Foxp3+T淋巴细胞百分率.结果 SLE患者异基因骨髓MSC移植后1周外周血CD4+Foxp3+T淋巴细胞百分率(4.8±1.6)%和移植后3个月(6.0±2.6)%均较移植前(2.1±1.2)%明显升高(5例,P<0.05).正常骨髓MSC与SLE患者PBMC共培养后CD4+Foxp3+T淋巴细胞百分率明显升高(P<0.05).且存在剂量依赖性,狼疮MSC也可上调SLE患者CD4+Foxp3+T淋巴细胞水平,但作用较正常MSC弱(P<0.05);正常MSC培养上清也可上调SLE患者PBMC中CD4+Foxp3+T淋巴细胞水平,但作用弱于MSC:PBMC=1:1组(P<0.05).MRL/Ipr鼠经1次或3次脐带MSC移植后脾脏CD4+Foxp3+T淋巴细胞百分率均较对照组高(P<0.05),但淋巴结CD+Foxp3+T淋巴细胞百分率均较对照组低(p<0.01),1次和3次移植组间差异无统计学意义.结论 异基因甚至异种MSC移植可上调SLE患者或MRL/Ipr鼠CD4+Foxp3+T淋巴细胞水平,同时体外试验也得出相同结论,且体外上调作用呈一定剂量依赖性,CD4+Foxp3+T淋巴细胞水平上调可能是MSC移植治疗SLE有效的机制之一.     

系统性红斑狼疮患者外周血CD4+CD25highFoxp3+调节性T细胞数量和Foxp3mRNA的表达水平与疾病活动性的相关性

目的 研究系统性红斑狼疮(SEE)患者CD4+CD25highFoxp3+调节性T细胞的数量及其功能基因Foxp3 mRNA的表达水平与SLE疾病活动性和肾脏损伤的相关性.方法 采用四色流式细胞术以Foxp3-异硫氰酸荧光素(FITC )/CD25-藻红蛋白/CD4-多甲藻叶绿素蛋白(PerCP)/CD3-藻蓝蛋白7抗体组合检测40名健康对照者及42例SLE患者外周血CD4+CD25highFoxp3+调节性T细胞的数量,实时荧光定量聚合酶链反应(PCR)检测特异性转录因子Foxp3 mRNA的表达水平,并分析其与SLE患者疾病活动指数(SLEDAI)、补体C3及血清抗双链DNA(dsDNA)抗体的关系.统计学方法采用t检验和Spearman相关分析.结果 活动期SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量显著低于健康对照组[(4±3)％与(7±4)％,P＜0.05],稳定期与健康对照组差异无统计学意义(P＞0.05);活动期SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量及CD4+CD25highFoxp3+调节性T细胞/CD4+比值显著低于稳定期患者[(4±3)％,(9±6)％与(5±4)％,(10±6)％,P均＜0.05];活动期SLE患者外周血Foxp3 mRNA的表达水平明显低于稳定期和对照组(P＜0.01,P＜0.05);SLE患者并发肾病组外周血CD4+CD25highFoxp3+调节性T细胞数量及CD4+CD25highFoxp3+调节性T细胞/CD4+比值显著低于SLE非肾病组(P＜0.05).相关分析显示,SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量与SLEDAI呈负相关(r=-0.5782,P＜0.05);CD4+CD25highFoxp3+调节性T细胞/CD4+比值与SLEDAI呈负相关(r=-0.4913,P＜0.05),与补体C3呈正相关(r=0.3687,P＜0.05);SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量与Foxp3 mRNA的表达水平呈正相关(r=0.6142,P＜0.0l).结论 SLE患者外周血CD4+CD25highFoxp3+调节性T细胞和Foxp3 mRNA的变化可能是导致SLE疾病发生和发展的关键因素之一,与疾病的活动性有密切关系.     

系统性红斑狼疮患者外周血淋巴细胞穿孔素表达及糖皮质激素对穿孔素的影响

目的 研究系统性红斑狼疮(SLE)患者外周血淋巴细胞穿孔素(PF)表达与分布,PF水平与疾病活动的相关性,探讨PF在SLE发病机制中的作用,观察糖皮质激素治疗对PF表达的影响.方法 SLE活动期患者16例,健康对照者12名.用流式细胞仪检测外周血淋巴细胞PF、CD3、CD4或CD8表达,用直线相关分析PF水平与SLE疾病活动性评分(SLEDAI)的相关性;比较糖皮质激素治疗前后PF水平变化.结果 与健康对照组比较,SLE活动期患者组外周血PF+淋巴细胞的百分率显著增高(P<0.01),PF的平均荧光强度(PFMFI)增高(P<0.01),PF+CD8+CD3+淋巴细胞的百分率明显增加(P<0.01),差异均有统计学意义.SLE活动期患者外周血PP淋巴细胞百分率与SLEDAI呈正相关(r=0.673).经过短期大剂量糖皮质激素治疗,SLE活动期患者外周血淋巴细胞PF+细胞百分率和PFMFI都显著下降(P<0.05),差异有统计学意义.结论 SLE活动期患者PF高表达,主要分布于CD8+CD3+细胞;PF水平与SLE活动程度呈正相关;短期糖皮质激素治疗能够减少患者体内PF表达.     

CD4+CD25-Foxp3+T淋巴细胞的表型鉴定及其在初发系统性红斑狼疮中的意义

目的 对初发系统性红斑狼疮(SLE)患者外周血异常表达CD4+CD25-Foxp3+T淋巴细胞进行表型鉴定,并探讨其临床意义.方法 对初发SLE患者外周血CD4+T淋巴细胞进行细胞表面分子[CD25、CD127、CCR4、糖皮质激素诱导的肿瘤坏死因子受体(GITR)、细胞毒T淋巴细胞相关抗原4(CT-LA-4)]和胞内分子(Foxp3)标染,流式细胞仪检测,并研究CD4+各细胞亚群与狼疮肾炎和疾病活动度(SLEDAI)相关性.结果 SLE患者外周血CD4+CD25-Foxp3+T淋巴细胞表面 GITR、CTLA-4和CCR4表达率与活化T淋巴细胞(CD4+CD25+Foxp3-)相比差异无统计学意义(P均>0.05),而显著低于调节性T淋巴细胞(CD4+CD25+Foxp3+)(P均<0.01);CD4+Foxp3+CD25high,CD4+Foxp3+CD25low和CD4+Foxp3+CD25-细胞中CD127low-百分率分别为(93.8±,3.5)%,(93.7±2.3)%,(92.0±2.1)%,三者之间差异无统计学意义(P>0.05);在CD4+细胞亚群中,当CD127low-时,Foxp3+在CD25high,CD25low和CD25-中表达率分别为 (91.4±2.6)%,(71.9±3.3)%,(9.0±2.2)%,三者之间差异均有统计学意义(P<0.01);SLE患者外周血CD4+CCR4+CD25highT淋巴细胞百分率与SLEDAI呈显著负相关(r=-0.695,P<0.001),狼疮肾炎患者(1.10±0.17)%显著低于SLE无肾炎组[(1.61±0.23)%,P<0.01]和健康对照组[(1.75±0.10)%,P<0.01];狼疮肾炎患者外周血CD4+ CCR4+CD25low-T淋巴细胞百分率显著高于健康对照组[(11.5 ±2.3)%与(8.0±1.0)%,P<0.01)].结论 初发SLE中异常升高的CD4+CD25-Foxp3+T淋巴细胞的表型类似早期活化效应T淋巴细胞.可以用CD4+CD25highCD127low-T淋巴细胞替选CD4+CD25highFoxp3+调节性T淋巴细胞.CCR4+调节性T淋巴细胞可能参与狼疮肾炎发病.     

初发系统性红斑狼疮患者外周血CD4+调节性T细胞CD73表达

目的 研究CD73在初发活动性系统性红斑狼疮(SLE)患者外周血CD4+调节性T细胞的表达情况,探讨其在SLE发病中的作用.方法 采用流式细胞术检测29例初发未经治疗的活动期SLE患者(SLE组)和22例健康人(健康对照组)外周血CD4+CD25+CD73+T细胞百分率及CD4+CD73+、CD4+CDhi25、CD4+CD25+T细胞中叉头状转录因子3(FOXP3)蛋白表达,同时对CD73表达水平与SLE活动指标进行相关性分析.结果 SLE组患者外周血CD4+ CD25+ CD73+T细胞百分率低于健康对照组[(1.25±1. 32)%vs(2.35±1.09)%,P＜0.01].SLE组和健康正常对照组,CD73在C4+ CDhi25T细胞的表达水平[(29.05±12.53)%、(43.35±10.09)%]高于CD4+ CD25+T细胞[(17.48±6.92)%、(29.98±10.39)%,P＜0.001];FOXP3蛋白在CD4+ CD73+ T细胞[(65.36±14.40)%、(63.80±14.05)%]、CD4+ CDhi25 T细胞的表达水平[(67.30±13.04)%、(56.30±9.21)%]明显高于CD4+ CD25+ T细胞[(45.70±12.74)%、(43.98±5.17)%,P＜0.001],在CD4+ CD73-T细胞几乎不表达,而在CD4+ CD73+ T细胞、CD4+ CDhi25 T细胞中的表达差异无统计学意义(P值均大于0.05).CD73在CD4+ CD25+ T细胞的表达水平与SLE疾病活动指数、ESR、C反应蛋白、抗补体C1q、抗核小体抗体均无相关性(P＞0.05).结论 CD73可作为调节性T细胞新的表面标记,其在调节性T细胞中的异常表达可能参与SLE的发病机制.     

L-选择素在系统性红斑狼疮患者外周血CD4~+CD25~+T淋巴细胞的表达及其与Foxp3的相关性

目的了解黏附分子L-选择素(L-selectin,CD62L)在系统性红斑狼疮(systemic lupus erythematosus,SLE)患者外周血CD4+CD25+T淋巴细胞的表达,及其与CD4+CD25+Treg细胞转录因子Foxp3的相关性。方法用流式细胞仪检测68例SLE患者外周血CD4+、CD4+CD25+T淋巴细胞CD62L和Foxp3的表达。根据SLEDAI评分,68例SLE患者中活动组36例,稳定组32例;健康对照组35人。结果活动组SLE患者外周血CD4+CD25+CD62L+T淋巴细胞为(1.71±1.60)%,低于对照组的(5.87±3.03)%(P0.01)和稳定组的(4.91±1.69)%(P0.01),差异具有显著性意义;且与SLEDAI呈负相关(r=-0.695,P=0.000),与补体C3水平呈正相关(r=0.522,P=0.000)。活动组SLE患者外周血CD4+CD25+CD62L+Foxp3+T淋巴细胞为(1.06±0.47)%,低于对照组的(3.17±0.87)%(P0.01)和稳定组的(3.46±1.15)%(P0.01),差异有显著性意义。CD4+T淋巴细胞CD62L的表达与CD4+CD25+T淋巴细胞CD62L和Foxp3的表达呈负相关(r=-0.689,P=0.000;r=-0.568,P=0.000);CD4+CD25+T淋巴细胞CD62L的表达与Foxp3的表达呈正相关(r=0.891,P=0.000)。结论CD62L在SLE患者外周血CD4+CD25+T的低表达及与Foxp3表达密切相关,可能在SLE发病中起着重要作用。     

系统性红斑狼疮患者CD4~+CD25~+CD127~(low/-)调节性T细胞中Foxp3的表达及免疫抑制功能研究

目的 研究系统性红斑狼疮(SEE)外周血中调节性T细胞不同标志以及调节性T细胞在SLE发病中的作用;探讨CD127与Foxp3的相关性,明确CD127定义调节性T细胞的特异性;鉴定CD4~+CD25~+CD127~(low/-)T淋巴细胞免疫抑制功能.方法 ①采用四色直接荧光素标记法和多参数流式细胞术检测40例SLE患者(19例初发和21例缓解)及15名健康对照外周血CD4~+CD25~+T淋巴细胞、CD4~+CD25~+CD127~(low-)T淋巴细胞、CD4~+CD25~+Foxp3~+T淋巴细胞、CD4~+CD25~(high)T淋巴细胞、CD4~+CD25~(high)CD127~(low/-)T淋巴细胞、CD4~+CD25~(high)Foxp3~+T淋巴细胞以及CD4~+CD127~(low/-)Foxp3~+T淋巴细胞占CD4~+T淋巴细胞的比率,并且将7种调节性T细胞比率与外周血抗双链DNA(dsDNA)等抗体及SLE疾病活动指数(SLEDA1)评分等进行相关性分析.②以流式细胞分选术结合细胞培养技术,检测和分析3例SLE患者和4名健康人外周血中CD4~+CD25~+CD127~(low/-)调节性T细胞对CD4~+CD25~-效应性T细胞增殖的抑制作用.采用两样本均数的t检验,重复测量的方差分析,Pearson相关与Spearman相关分析进行统计学处理.结果 ①SLE患者组7种调节性T细胞比率分别为(6.1±1.7)%,(3.1±1.3)%,(2.1±1.0)%,(1.6±0.3)%,(0.97±0.28)%,(0.69±0.23)%和(0.71±0.35)%.与健康对照组比较:SLE患者组前6种调节性T细胞比率均低于健康对照组(P<0.05).②SLE患者组:CD4~+CD25~+Foxp3~+、CD4~+CD25~(high)Foxp3~+T淋巴细胞比率与IgA呈正相关;CD4~+CD25~(high)CD127~(low/-)T淋巴细胞比率与抗SSB抗体呈正相关.③SLE患者初发组和缓解组比较:SLE患者初发组7种调节性T细胞中除CD4~+CD127~(low/-)Foxp3~+T淋巴细胞比率外,其余均低于缓解组(P<0.05).④SLE患者初发组治疗前后比较:激素治疗前6种调节性T细胞比率均低于激素治疗后(P<0.05).⑤SLE患者初发组、缓解组和对照组中,CD4~+CD25~+T淋巴细胞及CD4~+CD25~(high)T淋巴细胞中Foxp3的表达与CD127低表达均呈正相关.⑥SLE患者、健康人CD4+CD25-效应性T细胞的体外增殖都可以被自身CD4~+CD25~+CD127~(low/-)调节性T细胞所抑制,但SLE患者的抑制率明显低于健康对照.结论 SLE的免疫异常可能与调节性T细胞的数量和功能缺陷有关;CD127可能代替Foxp3作为调节性T细胞特异性的表面标记物.     

心肌梗死患者CD4~+CD25~+Foxp3~+ T细胞检测及意义

目的探讨心肌梗死患者外周血CD4+CD25+Foxp3+T细胞的水平及意义。方法采用流式细胞分析法,检测20例急性心肌梗死患者(AMI组)、21例陈旧性心肌梗死患者(OMI组)和36例健康体检者(对照组)外周血CD4+CD25+Foxp3+T细胞水平。结果 AMI组、OMI组的CD4+CD25+T细胞/CD4+T细胞比例分别为(7.20±1.96)%和(7.55±1.77)%均低于对照组的(8.81±1.50)%(P0.05);CD4+CD25+Foxp3+T细胞/CD4+T细胞比例AMI组为(1.42±0.38)%和OMI组为(1.46±0.55)%均比对照组(1.75±0.58)%低(P0.05)。结论 CD4+CD25+调节性T细胞比例降低可能打破了外周免疫耐受,参与了心肌梗死患者动脉粥样硬化的发生发展。     

CD3+CD56+自然杀伤T细胞在系统性红斑狼疮中的检测及意义

目的 检测系统性红斑狼疮(SLE)患者外周血中自然杀伤T细胞(NKT)的表达,探讨其与SLE疾病活动的关系.方法 入选确诊的SLE患者30例及健康对照30名,采用流式细胞仪检测外周血CD3+D56+NKT细胞的表达,分析NKT细胞的表达与SLE疾病活动评分和免疫学指标的相关性,采用两样本均数的t检验和Pearson相关分析进行统计学处理.结果与健康对照(4.16±0.22)%相比,SLE患者外周血中CD3+CD56+比例(2.53±0.33)%显著降低,NKT值与血清IgG水平、抗双链DNA抗体定量及SLE疾病活动指数(SLEDAI)评分呈负相关(r值=-0.595,-0.408,-0.637;P均<0.05).结论 SLE患者外周血中NKT细胞表达下降,其下降与SLE的疾病活动存在相关性.     

尖锐湿疣患者外周血Foxp3+CD4+CD25+调节性T细胞的检测及意义

目的 了解尖锐湿疣患者外周血Foxp3+CD4+CD25+调节性T细胞的表达水平,探讨其在尖锐湿疣发生发展机制中的作用.方法 分别收集30例尖锐湿疣患者(复发15例,初发15例)及20例健康者外周抗凝静脉血,分离出外周血单个核细胞.藻红蛋白(PE)标记抗CD4单抗,异硫氰酸荧光素(FITC)标记抗CD25单抗,细胞破膜后PE标记的抗Foxp3单抗行细胞内染色,三色流式细胞术分析Foxp3+CD4+CD25+调节性T细胞比例.组间比较采用ANOVA检验.结果外周血中Foxp3+CD4+CD25+调节性T细胞水平在尖锐湿疣患者组为(3.4±1.0)%,在复发组为(4.7±1.2)%,均显著高于健康对照组的(1.2±0.5)%(P<0.01).外周血Foxp3+CD4+CD25+调节性T细胞水平在初发组为(2.1±1.0)%,高于健康对照组,但差异无统计学意义,而在复发组明显高于初发组(P<0.05).结论 尖锐湿疣患者外周血Foxp3+CD4<"+>CD25+调节性T细胞数量增加,这种细胞免疫功能失调可能与其免疫学发病机制有关.     

Altered erythrocyte Na+ + K+ pump in adolescent obesity

The number of $\text{Na}\text{K}$ pump units and the cation transport activity of the pump were measured in erythrocytes from two etiologically different groups of obese adolescents and a group of normal controls. There was a significant reduction in the number of pump units, as measured by saturation ouabain binding, in erythrocytes from adolescents with idiopathic, early onset obesity. Individuals whose obesity developed subsequent to the appearance of a variety of hypothalamic lesions showed no reduction in the red cell complement of $\text{Na}\text{K}$ pump when compared to controls and the cation transport activity of their cells was higher than both the controls and the subjects with idiopathic obesity. These results support data obtained in adults that reduced red cell $\text{Na}\text{K}$ pump levels are seen in a group of individuals with idiopathic obesity. They further suggest that such reductions are not likely to be secondary to the obese state per se.     

Transport of Mg2+ by Na+-Mg2+ exchange

Intracellular free Mg(2+) concentration is maintained at low levels by active extrusion from the cells. One of postulated mechanisms is the Na(+)-Mg(2+) exchange, which extrudes Mg(2+) in exchange with Na(+) influx. Although the Na(+)-Mg(2+) exchange activity has been reported in many types of cell, including neurons, details of molecular mechanisms are only poorly understood. In this chapter, we briefly will review our current knowledge on [1] stoichiometry of the Na(+)-Mg(2+) exchange, [2] interaction between the Na(+)-Ca(2+) exchange and the Na(+)-Mg(2+) exchange, [3] molecular biology of the Na(+)-Mg(2+) exchanger.     

Difference between human red blood cell Na+-Li+ countertransport and renal Na+-H+ exchange

Several laboratories have reported that the activities of sodium-lithium countertransport are increased in red blood cells from patients with essential hypertension. Based on the many similarities between this transport system and the renal sodium-proton exchanger, a hypothesis has been put forth in the literature that increased red blood cell sodium-lithium countertransport activity may be a marker for increased sodium-proton exchange activity in the renal proximal tubule. The present studies were designed to test the hypothesis that sodium-lithium countertransport in red blood cells from humans or rabbits is mediated by the same transport mechanism that mediates sodium-proton exchange in the renal brush border from those species. Similar to what has been reported for the rabbit, the present studies show that an amiloride-sensitive sodium-proton exchanger is present in human renal brush border vesicles. However, Na+-Li+ countertransport in human and rabbit red blood cells, assayed under several different conditions, was not inhibited by amiloride. In agreement with what has been reported for humans, the present studies show that extracellular proton-stimulated sodium efflux is inhibited by amiloride in rabbit red blood cells. These data demonstrate a difference (amiloride sensitivity) between the red blood cell sodium-lithium countertransporter and the renal brush border sodium-proton exchanger in humans and rabbits. These experiments detract from the hypothesis that increased red blood cell sodium-lithium countertransport activity in patients with essential hypertension is a marker for increased sodium-proton exchange activity in the renal brush border.     

Red blood cell Li+-Na+ countertransport, Na+-K+ cotransport, and the hemodynamics of hypertension

Red blood cell Li+-Na+ countertransport and Na+-K+ cotransport activities, home blood pressure, invasive systemic hemodynamics, and limb venous compliance were measured in 65 white men (23 normotensive, 22 borderline hypertensive, and 20 mild essential hypertensive subjects). Li+-Na+ countertransport activity was positively and significantly correlated with subject-determined home systolic blood pressure (r = 0.31, p less than 0.02) and with directly measured systolic (r = 0.29, p less than 0.02) and diastolic (r = 0.27, p less than 0.03) blood pressures in the hemodynamic laboratory, independent of potential confounding variables. Analysis of the hemodynamic determinants of blood pressure revealed a significant positive correlation of countertransport with vascular resistance (r = 0.30, p less than 0.02) but not with cardiac output or cardiac index. High red blood cell Na+-K+ cotransport activity was not independently associated with hypertension or with a characteristic hemodynamic pattern but was related to decreased venous compliance. Red blood cell Li+-Na+ countertransport deserves further study as a marker for the genetic substrate of human essential hypertension. Red cell Na+-K+ cotransport may be altered secondarily by factors related to high blood pressure and seems to be a valid marker for abnormalities of the venous system in hypertension.     

Ca2+-dependent structural rearrangements within Na+-Ca2+ exchanger dimers

Cytoplasmic Ca(2+) is known to regulate Na(+)-Ca(2+) exchanger (NCX) activity by binding to two adjacent Ca(2+)-binding domains (CBD1 and CBD2) located in the large intracellular loop between transmembrane segments 5 and 6. We investigated Ca(2+)-dependent movements as changes in FRET between exchanger proteins tagged with CFP or YFP at position 266 within the large cytoplasmic loop. Data indicate that the exchanger assembles as a dimer in the plasma membrane. Addition of Ca(2+) decreases the distance between the cytoplasmic loops of NCX pairs. The Ca(2+)-dependent movements detected between paired NCXs were abolished by mutating the Ca(2+) coordination sites in CBD1 (D421A, E451A, and D500V), whereas disruption of the primary Ca(2+) coordination site in CBD2 (E516L) had no effect. Thus, the Ca(2+)-induced conformational changes of NCX dimers arise from the movement of CBD1. FRET studies of CBD1, CBD2, and CBD1-CBD2 peptides displayed Ca(2+)-dependent movements with different apparent affinities. CBD1-CBD2 showed a Ca(2+)-dependent phenotype mirroring full-length NCX but distinct from both CBD1 and CBD2.     

Na+-Li+ countertransport in essential hypertension

Several studies on Na+-Li+ countertransport have reported higher rates in essential hypertensive than in normotensives, with a distribution pattern which is dependent on racial and ethnic background. However, it is not well established whether this abnormality in Na+ transport is associated with an abnormal clinical setting. In the present study we have performed a kinetic analysis of the interaction of the Na+-Li+ countertransport system with internal Na+ in erythrocytes from a sample of 72 essential hypertensives and 30 normotensive controls. A significant increase in mean values of the maximal rate of Li+-stimulated Na+ efflux (Vmax; 375.1 +/- 23.8 versus 213.7 +/- 8.5 mumol/l cells per h; mean +/- s.e.m.; Mann-Whitney test: U = 500; P less than 0.0001), as well as in the apparent affinity constant for internal Na+ (KNa; 10.03 +/- 0.08 versus 6 +/- 0.4 mmol/l cells; Mann-Whitney test: U = 718; P less than 0.0079), were observed in essential hypertensives with respect to normotensives. Using the 95% confidence interval of Vmax in normotensives as the normal range, 29 (40.3%) of the essential hypertensives exhibited values above the normal upper limit. The maximal rate (Vmax) and the internal Na+ content required for half-maximal stimulation (K50%) of Na+-K+ ATPase and outward Na+-K+ cotransport, and the rate constant of Na+ leak (KPNa) in this subset were similar to the values observed in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells

Rapamycin is an immunosuppressive compound that is currently used to prevent acute graft rejection in humans. In addition, rapamycin has been shown to allow operational tolerance in murine models. However, a direct effect of rapamycin on T regulatory (Tr) cells, which play a key role in induction and maintenance of peripheral tolerance, has not been demonstrated so far. Here, we provide new evidence that rapamycin selectively expands the murine naturally occurring CD4(+)CD25(+)FoxP3(+) Tr cells in vitro. These expanded Tr cells suppress proliferation of syngeneic T cells in vitro and prevent allograft rejection in vivo. Interestingly, rapamycin does not block activation-induced cell death and proliferation of CD4(+) T cells in vitro. Based on this new mode of action, rapamycin can be used to expand CD4(+)CD25(+)FoxP3(+) Tr cells for ex vivo cellular therapy in T-cell-mediated diseases.     

Red cells from the original JAL+ proband are also DAK+ and STEM+

Background The low‐prevalence Rh antigen, JAL, was named after the index case, Mr. J. Allen. Based on reactivity of seven multi‐specific sera with his RBCs, it was apparent that they express at least one additional low‐prevalence antigen. The purpose of this study was to investigate the other low‐prevalence antigen(s) on J. Allen’s RBCs. Methods Blood samples and reagents were from our collections. Hemagglutination and DNA analyses were performed by standard methods. Results Our DNA analyses confirmed the presence of RHCE*ceS(340T) in J. Allen and revealed the presence of RHCE*ceBI (ce 48C, 712G, 818T, 1132G) and RHD*DOL (509T, 667T). RBCs from J. Allen were agglutinated by anti‐JAL, anti‐STEM, and anti‐DAK. Two of the reactive multi‐specific sera reported in the original paper reacted with RBCs from J. Allen, and with RBCs from four other people with RHCE*ceBI, including the original STEM+ index case (P. Stemper) but not with RBCs with the DIIIa, DAK+ phenotype. We conclude that they contain anti‐STEM. Conclusion J.Allen’s RBCs express the low‐prevalence Rh antigens, JAL, V/VS (extremely weakly), STEM, and DAK. The presence of JAL on the variant Rhce, RhceJAL (16Cys, 114Trp, 245Val), STEM on the variant Rhce, RhceBI (16Cys, 238Val, 273Val, 378Val), and DAK on the variant RhD (170Thr, 223Val), encoded by RHD*DOL in trans to RHCE*ceBI is consistent with expression of these antigens. When J. Allen RBCs are used to detect and identify an anti‐JAL, it is important to remember that they also express STEM and DAK.