初发过敏性紫癜患儿外周血CD4+CD28-和CD8+CD28-T细胞水平变化及意义

目的 观察初发过敏性紫癜(HSP)患儿外周血T淋巴细胞亚群(CD4+ CD28-T细胞和CD8+ CD28-T细胞)的表达变化,并探讨其临床意义.方法 采用流式细胞技术(FCM)检测89例初发HSP患儿(HSP组)和30例健康儿童(对照组)外周血T淋巴细胞免疫表型.结果 HSP组CD4+ CD28+、CD8+ CD28+、CD3+ CD4+T淋巴细胞表达水平及CD4+/CD8+比率较对照组显著降低(P均＜0.05);HSP组CD3+和CD3+ CD8+T淋巴细胞表达水平与对照组相比无显著性差异(P＞0.05);HSP组CD4+ CD28-T细胞和CD8+ CD28-T细胞较对照组明显增高(P均＜0.05),但在皮肤型、关节型、腹型、混合型和紫癜性肾炎五种临床类型间无明显差别(P均＞0.05).结论 HSP患儿存在T淋巴细胞亚群的紊乱,CD4+ CD28-T细胞及CD8+ CD22-T细胞的异常增高可能参与了其发病过程,但与HSP临床类型无关.     

急性冠状动脉综合征患者的CD4+CD28null T淋巴细胞电压门控性Kv1.3钾通道数量增加

目的 运用膜片钳技术检测急性冠状动脉综合征(ACS)患者的CD4+CD28nullT淋巴细胞Kv1.3钾通道的数量是否增加,探讨CD4+CD28nullT淋巴细胞上Kv1.3钾通道的表达.方法 选择17例ACS患者,11例年龄、性别匹配的正常体检者作为对照.运用荧光染色标记及膜片钳技术检测单个T淋巴细胞(CD4+CD28nullT淋巴细胞和CD4+CD28+T淋巴细胞)上Kv1.3钾通道的数量,比较Kv1.3通道在两种细胞上的差别.结果 ACS患者的CD4+CD28nullT淋巴细胞比例为(6.97±2.05)%,明显高于对照组的(1.38±0.84)%(P<0.05).ACS患者的CD4+CD28nullT淋巴细胞数量与hsCRP浓度呈正相关(r=0.52,P<0.05).ACS患者CD4+CD28nullT淋巴细胞Kv1.3通道的电导、密度、数量明显高于对照组CD4+CD28+T淋巴细胞(P<0.01).而两组CD4+CD28+T淋巴细胞间Kv1.3通道的电导、密度、数量差异无统计学意义(P>0.05).结论 ACS患者CD4+CD28nullT淋巴细胞明显增多.ACS患者CD4+CD28nullT淋巴细胞上Kv1.3钾通道数量比自身和对照的CD4+CD28+T淋巴细胞明显增多,CD4+CD28nullT淋巴细胞的功能可能与Kv1.3钾通道增多相关.     

同型半胱氨酸、高血压、颈内动脉粥样硬化易损斑块及T淋巴细胞亚群的关系研究

目的探讨同型半胱氨酸(Hcy)、高血压、颈内动脉粥样硬化易损斑块及T淋巴细胞亚群的关系。方法选取在我科住院治疗的高血压合并颈动脉粥样硬化斑块患者243例为研究对象,根据Hcy水平,将患者分为H型高血压组(162例,Hcy15 mmol/L)和非H型高血压组(81例,Hcy≤15 mmol/L)。根据患者Hcy水平以及颈动脉斑块类型,将患者分为H型高血压+易损斑块组(HHT+易损组,36例)、H型高血压+稳定斑块组(HHT+稳定组,126例)、非H型高血压+易损斑块组(HT+易损组,5例)、非H型高血压+稳定斑块组(HT+稳定组,76例)。对H型和非H型高血压组患者颈动脉易损斑块的发生率,四组(HHT+易损组、HHT+稳定组、HT+易损组、HT+稳定组)患者的Hcy水平及T淋巴细胞亚群进行比较分析;对高血压并颈动脉粥样硬化患者的Hcy水平与T细胞亚群的关系进行Spearman相关分析。结果 HHT组患者颈动脉易损斑块的发生率(22.2%)显著高于HT组患者(6.2%),差异有统计学意义(P0.05)。HHT+易损组患者的Hcy水平、外周血CD3~+T细胞比例、CD3~+CD4~+T细胞比例、CD3~+CD4~+/CD3~+CD8~+比值均显著高于其余三组,CD3~+CD8~+ T细胞比例明显低于其他三组,差异有统计学意义(P0.05)。HHT+稳定组患者的Hcy水平、CD3~+T细胞比例、CD3~+CD4~+T细胞比例、CD3~+CD4~+/CD3~+CD8~+比值均显著高于HT+易损组及HT+稳定组,CD3~+CD8~+T细胞比例明显低于HT+易损组及HT+稳定组患者,差异有统计学意义(P0.05)。HT+易损组、HT+稳定组患者的Hcy水平及T淋巴细胞亚群比较,差异无统计学意义(P0.05)。高血压合并颈动脉粥样硬化斑块患者的血Hcy浓度水平与其CD3~+CD4~+T细胞比例呈正相关(r=0.397,P0.05),与CD3~+CD8~+T细胞比例呈负相关(r=-0.411,P0.05),与CD3~+CD4~+/CD3~+CD8~+比值呈正相关(r=0.465,P0.001)。结论在高血压并颈动脉粥样硬化患者中,H型高血压患者颈动脉易损斑块的发生率较高,随着Hcy浓度升高,CD4~+T细胞比例升高,CD8~+T细胞比例下降,CD3~+CD4~+/CD3~+CD8~+比值增高,免疫紊乱趋向严重,有可能会促进颈动脉易损斑块的形成。     

系统性红斑狼疮患者外周血CD4+ CD8+和CD22+淋巴细胞活化分子CD69的表达

目的探讨系统性红斑狼疮(SLE)患者外周血淋巴细胞(PBL) T细胞(CD4+、CD8+)和B细胞(CD22+)活化分子CD69的表达.方法应用双染色流式细胞术检测CD4、CD8、和CD22细胞亚群CD69分子;在植物凝集素(PHA)刺激后20 h淋巴细胞亚群CD69分子的表达.结果①SLE患者PBMC的CD69分子活动期高于静止期(P＜0.001)和正常对照组(P＜0.01)的表达,SLE静止期患者与正常对照组CD69表达差异无显著性(P＞0.05).②进一步分析CD4+、CD8+和CD22+淋巴细胞亚群的CD69的表达,其中,SLE活动期患者CD4+细胞的CD69表达显著高于静止期(P＜0.001)和正常对照组(P＜0.01)的表达,SLE静止期患者与正常对照组CD69表达差异无显著性(P＞0.05);CD8+细胞活动期高于静止期患者(P＜0.05),其余组间差异无显著性(P＞0.05);CD22+B细胞各组间差异无显著性.③PHA刺激20 h后,CD4+、CD22+B细胞的CD69表达,活动期显著高于静止期患者和正常对照组(P＜0.01).结论 SLE患者外周血CD4+T细胞和CD22+B细胞存在着异常的活化,这种淋巴细胞的异常活化是SLE重要的发病机制之一.     

急性冠状动脉综合征患者外周血CD4~+及CD4~+ CD28~(null) T细胞活化后IKCa1通道的表达及意义

目的:研究急性冠状动脉综合征(ACS)患者外周血中CD4+T细胞及CD4+CD28null亚型活化前后IKCa1钾通道数目的变化以及IKCa1钾通道阻滞剂对活化CD4+T细胞效应分子表达的影响,探讨IKCa1钾通道对不稳定斑块的意义.方法:用免疫磁珠法分离出24例ACS患者外周血中的CD4+T细胞,其中12例进一步分出亚型CD4+CD28nullT细胞,采用全细胞膜片钳技术记录细胞活化前及活化3 d后的IKCa1钾电流.CD4+T细胞活化3 d后分别加入终浓度为0 2、1、5 μmol/L特异性IKCa1钾通道阻滞剂TRAM-34,再继续活化3 d,用反转录-PCR法检测干扰素-γ及颗粒酶B mRNA的表达.结果:活化后CD4+、CD4+CD28nullT细胞的IKCa1通道数目分别增加了9倍和8倍[活化前后2种细胞的通道数分别为(45±3)∶(439±33), (56±4)∶(497±45),均P<0 01].2种细胞的通道密度也分别增加了约3倍(P<0 01).活化前及活化后2种细胞的通道数目及通道密度均无差别.不同浓度的TRAM-34均下调CD4+T细胞活化后干扰素-γ、颗粒酶B mRNA的表达,各浓度组间干扰素-γ、颗粒酶B mRNA的表达差异均有统计学意义(P<0 01),浓度越高,各mRNA表达越低.结论:ACS患者外周血CD4+及CD4+CD28nullT细胞活化后IKCa1的通道数目及通道密度均明显增加,特异性IKCa1通道阻滞剂TRAM-34呈浓度依赖性地抑制CD4+T细胞活化时干扰素-γ及颗粒酶B mRNA的表达,提示CD4+T细胞的IKCa1钾通道可作为预防动脉粥样斑块不稳定的潜在治疗靶点.     

溃疡性结肠炎外周血CD3~+、CD4~+、CD8~+ T细胞的活化及其与炎症标志物的关系

目的研究溃疡性结肠炎(ulcerative colitis,UC)患者外周血CD3+、CD4+、CD8+T细胞变化与炎症相关指标的关系。方法收集25例UC患者和7名健康对照者外周血,用流式细胞仪检测CD3+、CD4+、CD8+T细胞的比例及表型,并与炎症相关指标(白细胞计数、血小板计数、血沉、CRP、白蛋白)进行相关性分析。结果 UC及活动期UC患者外周血CD3+、CD4+和CD8+T细胞的比例明显高于对照组,差异有统计学意义(P0.05);缓解期UC虽略高于对照组,但仅CD8+差异有统计学意义(P0.05)。UC患者白细胞计数、血小板计数、CRP和白蛋白明显高于对照组(P0.05);UC活动期的血小板计数、CRP、血沉和白蛋白水平明显高于健康对照组(P0.05)。CD3+、CD8+T细胞比例与CRP、血沉呈明显正相关,CD4+比例与CRP呈明显正相关(P0.05)。结论UC患者外周血T细胞活化,并与炎症相关指标CRP和血沉呈正相关。     

CD4~+CD25~+Treg细胞比例与老年动脉粥样硬化性脑梗死的相关性

目的探讨CD4~+CD25~+Treg细胞比例与老年动脉粥样硬化性脑梗死的相关性分析。方法老年动脉粥样硬化性脑梗死患者48例作为观察组,并将其根据颈动脉硬化程度分为轻度组(颈动脉内膜增厚),中度组(颈动脉斑块),重度组(颈动脉狭窄)三个亚组各16例。另取同期参加体检的健康老年志愿者48例作为对照组。通过流式细胞仪检测梗死7 d内观察组与对照组以及脑梗死不同亚组之间外周血CD4~+CD25~+Treg细胞比例,探究外周血CD4~+CD25~+Treg与颈动脉内-中膜厚度(IMT)的相关性。结果脑梗死后第1天和第2天观察组CD4~+CD25~+Treg细胞百分比均低于对照组,第5天至第7天高于对照组(均P<0.05),其余2 d差异无统计学意义(P>0.05)。脑梗死后第1~7天,三个亚组间CD4~+CD25~+Treg细胞百分比比较差异均有统计学意义(P<0.05),两两比较差异均有统计学意义(P<0.05)。观察组患者外周血CD4~+CD25~+Treg细胞百分比与IMT呈显著负相关(r=-0.543,P<0.05)。结论老年动脉粥样硬化性脑梗死患者急性期外周血CD4~+CD25~+Treg细胞百分比可作为评估脑缺血及血管内皮功能的非侵入性指标。     

CD4~+T细胞亚群与2型糖尿病发生发展的相关性研究

目的探讨CD4~+T细胞亚群与超重/肥胖、糖尿病前期及T2DM的关系。方法选取138例T2DM患者(T2DM组),156例糖尿病前期患者(pre-DM组)、84例超重/肥胖患者(OW/OB组)和72名健康体检者(NC组),研究各组CD4+T细胞亚群变化情况。结果 pre-DM组、T2DM组FPG、2hPG、C-P、FIns、HOMA-IR及高敏C反应蛋白(hsC-RP)均高于OW/OB组、NC组(P0.05)。T2DM组FPG、2hPG、C-P、FIns、TG、TC、HbA_1c、HOMA-IR及hsC-RP均高于pre-DM组(P0.05)。pre-DM组Th1、Treg细胞比例及Th1/Th2均低于OW/OB组及NC组(P0.05),Th2、Th17细胞比例高于OW/OB组、NC组(P0.05)。T2DM组Th1、Treg细胞比例低于pre-DM组(P0.05),Th2、Th17细胞比例高于pre-DM组、OW/OB组及NC组(P0.05)。Pearson相关性分析显示,2hPG、C-P、TC、HbA1c、HOMA-IR及hsC-RP与CD4~+T淋巴细胞相关参数有相关性(P0.05)。结论 T2DM及糖尿病前期患者存在CD4+T细胞亚群细胞比例失衡,CD4+T细胞亚群失衡状态在T2DM发生发展过程中可能起重要作用。     

抗病毒治疗HIV-1感染者外周血CD39~+ NK细胞的表达特点

目的通过分析接受长期抗病毒治疗(ART)的1型艾滋病病毒(HIV-1)感染者体内CD39~+NK细胞的频率和表型特征,探索其与主要临床指标的关系及临床意义。方法本研究入组10例健康对照(HCs)和28例长期接受ART的HIV-1感染者。利用流式细胞术检测NK细胞亚群分布以及NK细胞上CD39的表达情况,分析CD39+NK细胞亚群比例与CD4、CD8~+T淋巴细胞(简称CD4、CD8细胞)计数、以及CD4/CD8细胞比值的相关性。结果 28例长期接受ART的HIV-1感染者中,18例免疫重建成功患者(CRs)和10例免疫重建失败患者(INRs)。相较于HCs和CRs组,INRs组CD56dim亚群比例明显下降(平均值94.75%vs.82.65%,P 0.01;平均值93.20%vs.82.65%,P 0.001);INRs组CD39~+NK细胞的频率明显高于CRs组(平均值21.45%vs.7.79%,P 0.05)和HCs组(平均值21.45%vs.4.115%,P 0.001);长期接受ART的HIV-1感染者CD39+NK细胞占比与其CD4/CD8细胞比值呈负相关(r=-0.392 4,P=0.038 9)。结论免疫重建失败患者外周血中CD39+NK细胞表达频率明显高于免疫重建成功患者,HIV-1慢性感染者外周血CD39~+NK细胞表达增加伴随着CD4/CD8细胞比值的降低。     

共刺激分子CD28 CD152在类风湿关节炎患者T细胞亚群上表达异常的研究

目的观察共刺激分子CD28,CD152在类风湿关节炎(RA)患者的T细胞亚群上的表达异常情况,探讨RA的发病机制及治疗手段.方法用流式细胞仪采用直接免疫荧光法测定39例RA患者和20名健康对照人外周血T细胞表面标志CD3,CD4,CD8的表达情况及CD28,CD152在CD4+T和CD8+T细胞上的表达.结果 RA患者CD3+CD4+细胞较正常对照组显著增高(P＜0.01),CD3+CD8+细胞较正常对照组显著降低(P＜0.05),CD4+T细胞上CD28的表达较对照组显著降低(P＜0.05),而CD8+T细胞上CD28的表达与对照组差异无显著性(P＞0.05);CD4+T和CD8+T细胞上CD152的表达都较对照组显著增高(P＜0.01).结论在RA患者的细胞免疫活化过程中首先表现为B7/CD28信号途径占优势,T细胞被激活,激活的T细胞大量分泌CD152,它与CD28竞争结合B7分子,CD152/B7途径转而占优势,下调或终止T细胞反应.同时CD28+细胞数目的减少或功能缺陷造成RA患者外周血单个核细胞凋亡加速,是诱发RA患者的局部病理损害的原因.阻断CD152和B7的相互作用可增强特异性T细胞应答,为RA的免疫学治疗提供理论依据.     

Immunohistological patterns of myeloid antigens: tissue distribution of CD13, CD14, CD16, CD31, CD36, CD65, CD66 and CD67

Summary. A number of differentiation antigens on myeloid cells have been defined on the CD classification system by the four International Workshops on Human Leucocyte Differentiation Antigens. The distribution of eight of these antigens (CD13, CD14, CD16, CD31, CD36, CD65, CD66, CD67) have been studied in human tissues, with the aim of documenting their immunohistological patterns and their degree of myeloid restriction. CD13, the most widely distributed antigen, was found in skin, bile canaliculi, kidney and pancreas. CD14 was not restricted to monocytes and tissue macrophages, being also strongly expressed on dendritic reticulum cells. CD 16 was expressed on granulocytes and tissue macrophages (alveolar and Kupffer cells) and in the red pulp of the spleen. CD31 and CD36 gave a characteristic staining of vascular endothelium, corresponding to their identification as the platelet glycoproteins gp IIa and gp IV. Antibodies against the most recently defined myeloid antigens (CD65, CD66 and CD67) appeared to be more specific for myeloid differentiation than previously described 'myeloid antigens'.     

Precommitment of CD4+CD8+ thymocytes to either CD4 or CD8 lineages.

CD4+ and CD8+ mature T cells arise from CD4+CD8+ precursors in the thymus. During this process, cells expressing T-cell receptors (TCRs) reactive with self major histocompatibility complex (MHC) class I or II molecules are positively selected to the CD8 or CD4 lineage, respectively. It is controversial whether lineage commitment of CD4+CD8+ thymocytes is controlled directly by TCR specificity for MHC (instructional model) or, alternatively, by processes that operate independently of TCR specificity (stochastic model). We show here that CD4+CD8+ thymocytes bearing a MHC class I-restricted transgenic TCR can be subject to two alternative developmental fates. One population of CD4+CD8+ cells is positively selected by MHC class I molecules to the CD8 lineage as expected, whereas the other CD4+CD8+ population rearranges endogenous TCR genes and is positively selected by MHC class II molecules to the CD4 lineage. Blocking TCR-MHC class II interactions in vivo does not interfere with the generation of CD4+CD8+ cells expressing endogenous TCRs but does prevent their subsequent maturation to CD4+ cells. These data support a version of the stochastic model in which CD4+CD8+ thymocytes are precommitted to the CD4 or CD8 lineage independently of TCR specificity for MHC and prior to positive selection.     

急性脑梗死患者外周血CD4CD25 T细胞和CD4CD28~- T细胞的变化

目的探讨急性脑梗死患者外周血CD4CD25T细胞和CD4CD28-T细胞亚群的变化及意义。方法选择急性脑梗死患者22例(脑梗死组),另选取健康体检者18例(对照组);均采用流式细胞仪检测外周血CD4CD25T细胞和CD4CD28-T细胞占CD4T细胞比例。结果脑梗死组外周血CD4CD25T细胞/CD4T细胞比例明显低于对照组[(41.14±9.92)%vs(49.01±12.19)%,P<0.05],而CD4CD28-T细胞/CD4T细胞比例明显高于对照组[(19.93±15.60)%vs(11.96±8.60)%,P<0.05]。结论急性脑梗死患者外周血CD4CD25T细胞比例减少,而CD4CD28-T细胞升高,两者共同作用,可能在脑梗死发生、发展中起重要作用。调节T淋巴细胞亚群可能是脑梗死的潜在治疗靶点。     

Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.     

CD4+, CD33-, CD13-, CD14- acute monoblastic leukaemia.

We report a case of acute monoblastic leukaemia in which the expression of the CD4 antigen occurred in the absence of myeloid and monocytic lineage specific markers. Unexpected marker profiles have biological and diagnostic implications and we also suggest that the inappropriate expression of the CD4 antigen may be implicated in the poor prognosis of this case.     

Differential CD26-mediated activation of the CD3 and CD2 pathways after CD6-depleted allogeneic bone marrow transplantation

Patients who have undergone allogeneic bone marrow transplantation (allo-BMT) are susceptible to a variety of opportunistic infectious complications in the months to years after engraftment. Impaired in vitro T-cell functions have been documented in these patients, and these T-cell dysfunctions contribute to the prolonged immune deficiency after allo-BMT. In the present study, we examined the expression of CD26 as well as the reconstitution of CD26-mediated T-cell costimulation via the CD3 and CD2 pathways at various times in patients aged greater than 18 years after CD6-positive, T-cell depleted allo- BMT. We found that the percentage of CD26- and CD3-positive cells, as well as the levels of expression of both antigens, was lower than in normal controls during the first 4 months after CD6-depleted allo-BMT. Subsequently, the amount of lymphocytes expressing CD3 and CD26 and the quantitative surface expression of CD3 and CD26 were not significantly different in patients and normal controls. Functional studies showed that CD26-mediated T-cell proliferation via the CD3 pathway was considerably improved and almost reached normal levels by 1 year, whereas recovery of CD26-mediated T-cell proliferation via the CD2 pathway was delayed for at least 2 years after CD6-depleted allo-BMT. As CD26 involvement in the regulation of human thymocyte activation is restricted preferentially to the CD3 pathway--unlike its involvement with both CD3 and CD2 pathways of peripheral T cells--our results suggest that the different effects of CD26-mediated costimulation via the CD3 and CD2 pathways after CD6-depleted allo-BMT may be a reflection of peripheral T-cell immaturity in those individuals, similar to that seen in mature medullary thymocytes or cord T lymphocytes.     

The "ex vivo" patterns of CD2/CD7, CD57/CD11c,CD38/CD11b,CD45RA/CD45RO,and CD11a/HLA-DR expression identify acute/early and chronic/late NK-cell activation states

To define a dynamic sequence of phenotypic changes related to early and late phases of NK-cell activation, we have analyzed by four-color flow cytometry the immunophenotype of normal blood NK-cells from 12 healthy individuals and compared it with those from 15 patients with acute viral infections and 15 patients with either chronic infections or tumors. Although a great interindividual variability was found, nonstimulated CD56(+) NK-cells, present in normal blood samples, usually were CD2(-/+lo), CD7(+hi), HLA-DR(-), CD11b(+), CD38(+), CD11a(+hi), CD45RA(+hi), and CD45RO(-), the expression of CD11c and CD57 being heterogeneous and variable. Recently activated NK-cells, herein corresponding to NK-cells from patients with acute viral infections, displayed a pattern of expression of CD2/CD7 similar to that referred to above, but they typically showed higher levels of CD11a, CD38, and HLA-DR, as well as downregulation of CD11b and CD45RA, accompanied in some cases by coexpression of CD45RO; in addition, these NK-cells were CD11c(+) and CD57(-/+lo). Late-activated NK-cells, represented by NK-cells present in patients with chronic infections and tumors, converted into a CD2(+hi)/CD7(-/+lo) immunophenotype and expressed heterogeneously low levels of CD38 and CD11b; moreover, they were CD57(+) and CD11c(-/+). At this stage, most NK-cells had already reverted into their original CD45RA(+)/CD45RO(-)/HLA-DR(-) phenotype. In summary, we show that the patterns of expression of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR may help us to define the immunophenotypic profiles associated with early and late NK-cell activation phases in 'in vivo' models.     

CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells

The CD4 coreceptor is crucial in the activation of major histocompatibility complex (MHC) class II restricted CD4 (+) T lymphocytes by binding the same MHC class as the T-cell receptor (TCR) and by potentiating TCR-dependent signaling. CD4 is also expressed by invariant natural killer T cells (iNKT), which recognize natural and synthetic lipid antigens, such as alpha-galactosyl ceramide (alpha-GalCer), in association with the MHC class I-like CD1d molecule. Human iNKT cells can be divided into 2 major subsets depending on CD4 expression: CD4 (+) iNKT preferentially produce T-helper (Th)0/Th2 cytokines, whereas CD4(-) iNKT cells produce Th1 cytokines after antigenic activation. Cytokines produced by iNKT may have immunomodulatory roles in various physiopathologic contexts, but their mode of regulation by iNKT cells remains ill-defined. Using blocking reagents neutralizing CD4 binding, experimental systems where MHC class II molecules are absent and recombinant alpha-GalCer/CD1d complexes, we show that CD4 potentiates human iNKT cell activation by engaging CD1d molecules. These results indicate that the CD4 coreceptors may contribute to the fine tuning of iNKT cells reactivity.