CD44+/CD24-细胞在乳腺癌组织及细胞系中的数量与分布

目的 检测CD44+/CIY24-细胞在乳腺癌组织及细胞系中的分布及数量,探讨其与乳腺癌常用标志物表达和乳腺癌分子亚型的关系.方法 采用免疫组织化学SP双染及单染法,分别检测了60例乳腺浸润性导管癌中的CD44及C1724的共表达情况和ER、PR、HER2、人雌激素诱导蛋白PS2、bcl-2、nm23的单独表达情况,同时检测了三种乳腺痛细胞系(MCF-7、MDA-MB-468及MDA-MB-231)中CD44及CD24的表达情况.结果 不同病例标本中CD44+/C1724-细胞的数量差异较大,分布无明显规律,总阳性率为65.0%;CD44+/CD24-细胞数量与患者年龄、肿瘤大小、淋巴结转移情况及ER、PR、HER-2、人雌激素诱导蛋白PS2、bcl-2、nm23表达情况无关(P均>0.05);CD44+/CD24-细胞数量与乳腺癌分子亚型无关.CD44+/CIY24-细胞在MCF-7、MDA-MB-468及MDA-MB-231细胞系中的比例分别为<1%、5%及>80%.结论 CD44+/CD24-细胞存在于部分乳腺癌组织及细胞系中,其数量及分布与乳腺癌的分子亚型和临床病理参数无直接关系.     

肿瘤干细胞相关标记物CD44及CD24在乳腺癌中的表达及其意义

目的探讨肿瘤干细胞相关标记物CD44及CD24在乳腺癌组织中的表达特点、CD44+/CD24-细胞与HER-2、ER、PR、CK5/6表达的相互关系及其与临床病理因素的关系。方法采用免疫组化SP单染及双染法检测42例乳腺导管原位癌及126例乳腺浸润性导管癌组织中CD44及CD24的表达情况,检测126例乳腺浸润性导管癌组织中HER-2、ER、PR、CK5/6表达状况以进行免疫分型。结果 (1)CD44阳性定位于癌细胞膜。在浸润癌中阳性率为56.3%,在导管原位癌中阳性率为85.7%。两者差异有显著性意义(P<0.05)。在不同分化程度的乳腺浸润性癌中,CD44阳性率分别为69.2%、58.1%及44.7%,差异有显著性意义(P<0.05)。(2)CD24阳性表达于非癌性乳腺组织中小管的腔缘;在癌组织中除腔缘阳性外,可出现膜质阳性。在浸润癌中阳性率为32.5%,在导管原位癌中阳性率为64.3%。两者差异有显著性意义(P<0.05)。(3)126例浸润性导管癌中CD44+/CD24-者65例,占51.6%;CD44+/CD24-阳性细胞在Luminal A型为47.5%、Luminal B型为42.9%、HER-...     

CD44剪接变异体在乳腺癌中的表达

目的观察乳腺癌细胞系及原发性乳腺癌组织中CD44剪接变异体种类及其表达情况。方法 RT-PCR法检测乳腺癌细胞系MDA-MB-231、MDA-MB-435和20例原发性乳腺癌组织中CD44变异体表达情况,分析其与临床病理参数之间的关系。结果 RT-PCR分析显示,在已知的8种剪接变异体、乳腺癌细胞系MDA-MB-231、MDA-MB-435和所检测的全部乳腺癌组织标本中,检测到CD44剪接变异体1、2、3、4、5、6、8,其中CD44剪接变异体4、5表达水平较高。CD44剪接变异体与临床病理参数分析显示CD44剪接变异体与患者年龄、TNM分期、淋巴结转移、ER、PR表达无关。CD44剪接变异体1和CD44剪接变异体2 mRNA的高表达与较小的肿瘤直径有关;CD44剪接变异体4的mRNA高表达与组织学高级别有关;CD44剪接变异体2、6的mRNA高表达与Her-2低表达相关;CD44剪接变异体5的mRNA低表达和Her-2高表达相关。结论 MDA-MB-231、MDA-MB-435及所检测的乳腺癌组织标本中,CD44剪接变异体为异质性表达,以标准型CD44表达水平最高。     

CD44与乳腺癌的研究进展

CD44基因蛋白是一种细胞表面跨膜糖蛋白,属于黏附分子家族。CD44基因外显子根据表达方式可分为标准型CD44(CD44s)和变异型CD44(CD44v)两种类型。大量研究发现,CD44蛋白参与细胞-细胞、细胞-胞外基质之间的特异性粘附,CD44及其亚型在乳腺癌的异常表达可能与癌症的发生、发展和转移密切相关。此外,乳腺癌干细胞表面高度表达CD44分子,针对CD44分子与乳腺癌干细胞关系的研究,将会为临床上对乳腺癌的诊断、治疗选择以及预后预测提供更充分的理论依据。     

CD68和CD206阳性巨噬细胞在乳腺癌组织中的浸润及对预后影响

目的探讨乳腺癌间质中CD68~+和CD206~+肿瘤相关巨噬细胞(tumor associated macrophages,TAMs)的浸润与临床病理特征的关系及其对预后的影响。方法应用免疫组化Max Vision法检测172例乳腺癌和50例乳腺良性病变组织中CD68和CD206的表达,比较CD68~+TAMs和CD68~+/CD206~+TAMs浸润密度与乳腺癌临床病理特征的关系及其对预后的影响。结果CD68~+TAMs和CD68~+/CD206~+TAMs在乳腺癌的浸润密度均较良性病变组织升高(P均0.000 1);CD68~+/CD206~+TAMs高密度表达分别与肿瘤直径增大、淋巴结分期及临床分期增高等有关(P0.000 1,P=0.007,P0.000 1)。CD68~+/CD206~+TAMs高密度浸润组患者的无病生存率及总生存率均较低密度浸润组降低(P=0.013,P=0.003)。结论 CD68~+TAMs和CD68~+/CD206~+TAMs在乳腺癌组织中有较高的浸润密度,CD68~+/CD206~+TAMs可能与乳腺癌的发生、发展密切相关,并有望成为预测乳腺癌预后的重要潜在标志物。     

CD44和CD24在鼻咽癌细胞系HK-1中调控STAT3发生磷酸化的分子机制研究

目的 研究CD44和CD24在鼻咽癌细胞系HK-1中调控STAT3发生磷酸化的分子机制.方法 采用流式细胞仪对培养的鼻咽癌HK-1高分化NPC细胞进行分选以获得CD44 +/CD24+ HK1细胞及CD44-/CD24-HK1细胞,通过Western blot、MTT和肿瘤微球形成等实验,分析鼻咽癌阳性肿瘤细胞中P-STAT3的表达,以及STAT3被抑制剂Stattic沉默后,对CD44+/CD24+ HK1和CD44-/CD24-HK1细胞增值能力和肿瘤微球形成能力的影响.结果 鼻咽癌HK-1细胞中可以提取到34.7％的CD44 +/CD24+ HK1细胞和41.5％的CD44-/CD24-HK1细胞,CD44+/CD24+ HK1细胞比CD44 /CD24-HK1细胞表达磷酸化STAT3水平高.STAT3的抑制剂Stattic可以抑制CD44+/CD24+ HK1和CD44-/CD24-HK1细胞磷酸化STAT3的表达,MTT实验显示16μmol/L Stattic明显抑制CD44+/CD24+ HK1和CD44-/CD24-HK1细胞增殖,肿瘤微球形成实验表明Stattic可明显抑制CD44+/CD24+ HK1和CD44-/CD24-HK1细胞微球形成能力,即STAT3在CD44+/CD24+ HK1细胞增殖和鼻咽癌进程中发挥重要的作用.结论 CD44和CD24在鼻咽癌侧群细胞HK-1细胞中,CD44 +/CD24+阳性细胞通过诱导STAT3发生磷酸化来促进鼻咽癌发展,为鼻咽癌肿瘤干细胞的靶向治疗提供了新的靶点,临床治疗可靶向抑制STAT3的表达,从而抑制CD44+/CD24+ HK1细胞增殖和肿瘤微球的形成,最终达到降低鼻咽癌的发生率.     

不同类型乳腺组织中CD44~+/CD24~-细胞的数量与分布

目的检测CD44+/CD24-细胞在乳腺正常组织及良恶性肿瘤中的数量与分布特点,探讨其在乳腺癌发生、发展中的作用。方法采用免疫组化SP双染法,检测了30例乳腺正常组织(normal tissue,NT),30例乳腺纤维腺瘤(fibroadenoma,FA),60例乳腺浸润性导管癌(invasive ductal carcinoma,IDC)中的CD44及CD24的共表达情况。结果在乳腺NT及FA中,可见CD44+/CD24+,CD44+/CD24-,CD44-/CD24-3种表型,而在IDC中,除上述3种表型外,尚可见CD44-/CD24+表型。从NT,FA到IDC,CD44+/CD24-细胞的阴性率(-,阳性率1%)依次降低(40.0%→36.7%→35.0%);而强阳性率(,阳性率60%)依次升高(0.0→6.7%→21.7%)。结论 CD44+/CD24-可能作为一种阶段性祖细胞标记,参与了正常乳腺的分化及乳腺肿瘤的发展过程。     

在乳腺癌干细胞中Hedgehog信号通路相关基因表达增强

目的 了解Hedgehog信号通路在乳腺癌发生发展中的作用.方法 用免疫磁珠法从无血清培养的乳腺癌悬浮细胞中分选CD44+CD24-细胞和非CD44+CD24-细胞,用real-time RT-PCR法检测Hedgehog信号通路主要分子$HH、PTCH1、SMO和GLI1 mRNA在细胞中的表达,用免疫组织化学法检测上述因子在乳腺癌组织中的表达.结果 分选出的CD44+CIDA-细胞约占乳腺癌悬浮细胞总数的8.25%,分选出的CD44+CD24-细胞表达干细胞标志蛋白ALDHA1和Oct-4;SHH、PTCH1、SMO和GLI1 mRNA在CD44+CD24-细胞中的表达均高于其在非CD44+CD24-细胞中的表达(P＜0.05);SMO和GLI1蛋白在三阴性乳腺癌的表达均高于非三阴性乳腺癌组织(P＜0.05).结论 在乳腺癌干细胞CD44+CD24-细胞中Hedgehog信号通路被激活,抑制癌症干细胞中Hedgehog通路的活化可能会降低或阻止乳腺癌的复发及化疗耐受.     

乳腺癌中OPN、CD44v6及CD10的表达及其临床意义

目的探讨骨桥蛋白(osteopontin,OPN)、CD44v6、CD10在乳腺癌及腺病中的表达,分析三者与乳腺癌临床病理特征及预后的相关性。方法采用免疫组化En Vision两步法检测OPN、CD44v6、CD10在浸润性癌非特指型(153例)、导管原位癌(40例)、腺病(28例)中的表达;采用χ2检验分析三者与乳腺癌临床病理特征的关系,多因素分析采用Cox回归模型,预后分析采用Kaplan-Meier法,组间差异比较采用Log-rank检验。结果在腺病、导管原位癌、浸润性癌非特指型中,OPN阳性率分别为7.1%、27.5%、56.2%,CD44v6阳性率分别为10.7%、40.0%、57.5%,CD10阳性率分别为3.5%、37.5%、55.6%。三者在腺病中的阳性率均低于乳腺癌,差异具有统计学意义(P=0.020、0.042、0.003)。浸润性癌非特指型组织中OPN、CD44v6和CD10的表达均与组织学分级、淋巴结转移相关,且OPN、CD44v6表达均与p TNM分期相关,CD44v6表达与PR状态相关(P均0.05);在导管原位癌中三者的表达与核分级相关,差异均有统计学意义(P均0.05);三者的表达与患者年龄、绝经状态、脉管浸润、Ki-67增殖指数、ER状态、HER-2状态均无关(P均0.05)。OPN、CD44v6和CD10在乳腺癌中的表达两两间均呈正相关(P均0.001)。多因素分析提示淋巴结转移、CD10阳性是浸润性癌非特指型患者的预后影响因素。生存分析显示在浸润性癌非特指型中,三者均阴性组患者的无病生存率(disease-free survival,DFS)、总生存率(overall survival,OS)均优于三者均阳性组,差异有统计学意义(P=0.010、0.007)。结论 OPN、CD44v6、CD10在乳腺癌中高表达,均与乳腺癌进展相关。联合检测OPN、CD44v6、CD10在乳腺癌中的表达,对于判断患者预后具有重要价值。     

盐霉素通过TGFβ1/Smad信号通路抑制MMP-2、9降低CD44~+/CD24~(-/low)表型乳腺癌干细胞迁移和侵袭能力

目的分析盐霉素对CD44~+ /CD24~(-/low)表型乳腺癌干细胞迁移和侵袭能力的影响,并初步探讨其影响机制。方法通过有血清和无血清培养技术培养人乳腺癌MCF-7细胞株,收集两种细胞,对其CD24、CD44标志物进行荧光染色,采用流式细胞仪检测CD44~+ /CD24~(-/low)亚群细胞的比例;盐霉素培养MCF-7细胞株和CD44~+ /CD24~(-/low)表型乳腺癌干细胞,MTT法筛选出引起CD44~+ /CD24~(-/low)表型乳腺癌干细胞细胞凋亡低于IC50的浓度;Transwell技术检测MCF-7和CD44~+ /CD24~(-/low)表型乳腺癌干细胞的迁移和侵袭能力,以筛选出的浓度诱导CD44~+ /CD24~(-/low)表型乳腺癌干细胞,以排除盐霉素对该细胞增殖抑制作用的影响,Transwell技术检测该细胞迁移和侵袭能力的变化;Western blot技术检测TGFβ1、Smad2、Smad3、p-Smad2、pSmad3、MMP-2、MMP-9蛋白水平的变化。结果 CD44~+ /CD24~(-/low)表型乳腺癌干细胞在无血清培养和有血清培养中的比例分别为(86.93±0.53)%和(19.98±0.62)%(P0.01),CD44~+ /CD24~+ 表型细胞的比例分别是(12.68±0.59)%和(79.90±0.57)%(P0.01);MTT法筛选出低于IC50的浓度是1、3、5、7μmol/L;Transwell技术检测CD44~+ /CD24~(-/low)表型乳腺癌干细胞迁移和侵袭能力明显高于MCF-7细胞株,并随盐霉素浓度的上升呈下降趋势(P0.05)。Western blot技术检测TGFβ1、Smad2、Smad3、p-Smad2、p-Smad3、MMP-2、MMP-9蛋白水平下调(P0.01)。结论盐霉素可能通过TGFβ1/Smad信号通路下调MMP-2、MMP-9蛋白水平,从而降低CD44~+ /CD24~(-/low)表型乳腺癌干细胞迁移和侵袭能力。     

Chronic lymphocytic leukemia with peripheral T lymphocytes expressing CD 2+, CD 3+, CD 4-, CD 8-, CD 16+, and CD 56+ and lymph-node lymphocytes expressing CD 2+, CD 3-, CD 4-, CD 8-, CD 16+, CD 38+, and CD 56+]

A 33-year-old man was hospitalized because of thrombocytopenia and severe splenomegaly. On admission 78% of peripheral lymphoid cells were abnormally large, with pale cytoplasm. Flow cytometry of the abnormal lymphocytes showed that they expressed CD 2, CD 3, CD 11, CD 16, and CD 56, but not CD 4 nor CD 8, so they were T-cell large granular lymphocytes (T-LGL). Abnormal lymphocytes obtained from a lymph node expressed CD 2, CD 16, CD 38, and CD 56, but not CD 3, CD 4, and CD 8, so they were natural killer(NK) cells. Splenectomy was performed and the operative specimen showed diffuse infiltration of pleomorphic lymphocytes, probably chronic lymphocytic leukemia cells. After splenectomy, the platelet count returned to normal but the lymphocytosis continued. Two years after discharge, chemotherapy was done because of thrombocytopenia and hepatomegaly. The patient died of disseminated intravascular coagulation arising from sepsis. The differences and similarities between peripheral and lymph-node lymphocytes suggest that LGL and NK cells may be differentiated from the same kind of cell, somewhat differentiated from stem cells.     

Concentrations of Soluble CD95 and CD8 Antigens in the Plasma and Levels of CD8+CD95+, CD8+CD38+, and CD4+CD95+ T Cells Are Markers for HIV-1 Infection and Clinical Status

Apoptosis mediated via the CD95 (FAS/APO-1) receptor is thought to play a role in the depletion of CD4+ T cells in HIV infection. In the present study expression of the CD95 antigen on lymphocyte subsets and the plasma level of soluble CD95 (sCD95) were determined in HIV-1-infected adults. The expression of CD95 was increased on CD8 cells in all groups of HIV+ individuals, while increased expression of CD95+ cells on CD4 cells was limited to individuals with CD4 counts of <200 mm³. The proportion of CD4+ that expressed CD95 was inversely correlated with the percentage of CD4+ PBL. The concentration of sCD95 was significantly higher in the plasma of HIV-infected individuals than in normal controls. The level of sCD95 in HIV-infected subjects showed no correlation with the percentage of PBL expressing CD95, indicating that the increased level of sCD95 did not reflect release from CD95+ PBL. The plasma sCD95 concentration was significantly correlated with the percentage of CD8+ cells and, particularly, with CD8+CD38– cells. A striking inverse correlation was found between the sCD95 plasma concentration and the proportion of CD4+CD95+ cells out of the total CD4+ population. There was no correlation between the serum level of sCD95 and that of soluble CD8 (sCD8), both of which were increased in the plasma of HIV+ individuals. Unlike the level of sCD95, the level of sCD8 in the plasma of HIV+ individuals. Unlike the level of sCD95, the level of sCD8 in the plasma of HIV+ individuals was correlated with the percentage of CD95+ and CD8+CD38+ cells. The present study indicates that plasma sCD95 may be one of the factors that regulate apoptotic death of lymphocytes in HIV infection.     

Colocalization analysis of sialomucins CD34 and CD164

Flow cytometric protocols are employed to identify and characterize hemopoietic stem/progenitor populations before transplantation. Cell surface antigens, including CD34, are employed in this process and widely used in harvest protocols, which largely ignores the potential functional role of such antigens. Transmembrane glycoprotein sialomucins, including CD34 and CD164, have been implicated in cell-to-cell interactions and activation. CD164, also expressed on early hemopoietic populations, was reported to have a possible function facilitating CD34(+) cells to adhere to bone marrow stroma. In this study, we employed high-definition laser-scanning confocal microscopy to investigate CD34 and CD164 surface co-localization patterns on bone marrow and cord blood cells and to compare the expression patterns using a three-dimensional computer-generated method developed in house. Differential interference microscopy analysis revealed bone marrow membrane activity was higher than the corresponding cord blood counterpart, perhaps indicating the marrow microenvironmental nature. Fluorescence analysis of CD34 and CD164 antigens showed both were expressed first in a halo-like pattern and second in antigen-dense pockets. Three-dimensional computer analyses further revealed that this pocketing corresponded to dense crest-like surface structures appearing to rise from the point of adherence on the slide. Further, it was found that CD34 and CD164 display strong colocalization patterns on cells expressing both antigens. The dual nature of the CD34 and CD164 antigens discovered here lends further evidence to the previous literature implicating a strong functional link between these two sialomucins, which should be considered in the transplantation arena and in the function of such sialomucins as negative regulators of cell proliferation.     

CD28/CTLA-4 and CD80/CD86 families

T cell stimulation in the absence of a second, costimulatory signal can lead to anergy or the induction of cell death. CD28 is a major T cell costimulatory receptor, the coengagement of which can prevent anergy and cell death. The CD28 receptor is a member of a complex family of polypeptides that includes at least two receptors and two ligands. Cytotoxic lymphocyte-associated molecule-4 (CTLA-4, CD152) is the second member of the CD28 receptor family. The ligands or counterreceptors for these two proteins are the B7 family members, CD80 (B7-1) and CD86 (B7-2). This article reviews the CD28/CTLA4 and CD80/CD86 families, and outlines the functional outcomes and biochemical signaling pathways recruited after CD28 ligation.     

Kikuchi病中检测出全T细胞相关抗原丢失

目的 观察全T细胞相关抗原CD2、CD3、CD5、CD7在Kikuchi病中是否存在丢失,探讨将全T细胞相关抗原丢失作为鉴别T细胞良、恶性病变辅助诊断依据的局限性.方法 收集33例明确诊断为Kikuchi病和15例淋巴组织反应性增生病例,通过复习HE切片并应用免疫组织化学EliVision法检测病变中CD2、CD3、CD5、CD7的表达情况.结果 72.7％ (24/33)的Kikuchi病患者中存在一种或几种全T细胞相关抗原的丢失,其中13例仅CD5丢失,1例仅CD7丢失,1例仅CD2丢失,2例CD2和CD7丢失,4例CD5和CD7丢失,2例CD2和CD5丢失,1例CD2、CD5和CD7丢失.以CD5丢失最多见(60.6％,20/33),其次为CD7(24.2％,8/33)和CD2( 18.2％,6/33).抗原的丢失多见于增生型及坏死型.经随访,抗原的丢失与Kikuchi病的预后无明显相关性.15例淋巴组织反应性增生病例中无明显抗原丢失现象.结论 Kikuchi病中存在一种或几种全T细胞相关抗原的丢失.因此,将全T细胞相关抗原丢失作为T细胞淋巴瘤辅助诊断依据不适用于Kikuchi病.     

Mitogen-induced modulation of CD3, CD4, and CD8(1)

It is not clear whether CD3 contacts CD4 or CD8 directly, nor have the regulation and interregulation of expression of these three receptor molecules been determined. We explored these issues by first stimulating human peripheral blood lymphocytes in vitro with three well-characterized T-cell receptor-directed mitogens (phytohemagglutinin [PHA], concanavalin A [ConA], and anti-CD3 monoclonal antibody [alphaCD3]) and then using multiparameter flow cytometric techniques to investigate modulation of surface (sur) and cytoplasmic (c) CD3, CD4, and CD8. Cultures with alphaCD3 had a rapid, large, and persistent decline in surCD3; the cCD3 median fluorescent intensity (MFI) declined gradually, over the entire culture period. With alphaCD3, surCD4 MFI and cCD4 MFI declined by days 4 to 8 (31% of ex vivo value, p < 0.001 and 47%, p = 0.033), as did surCD8 MFI (58%, p = 0.010). PHA was associated with an increase in surCD8%, surCD8 MFI, and cCD8% at days 4 to 8 (178% of ex vivo, p = 0.003; 168%, p = 0.025; and 331%, p = 0.001). For PHA at days 4 to 8, cCD8 MFI was highly variable but always higher than in unstimulated cultures (5 of 5 experiments). With ConA, at 3 to 5 hours ex vivo, there was a decrease in surCD3 MFI relative to ex vivo (64%), surCD4% (83%), cCD4% (87%), surCD4 MFI (50%) and cCD4 MFI (48%), surCD8% (85%) and an increase in cCD8% (260%). As with PHA, at days 4 to 8, surCD8% was high relative to ex vivo (169%). Thus, we found that alphaCD3 had delayed effects on CD4 and CD8; PHA had delayed effects on CD8 only; and ConA had very rapid effects on CD3, CD4, and CD8, as well as a delayed effect on surface CD8. These effects involve both surface and cytoplasmic antigen expression and are more consistent with degradation or retention, rather than with shedding or increased production. They may reflect direct interactions between CD4 or CD8 and CD3 and/or interregulation of CD3 expression with expression of these coreceptor molecules.     

A CD44 monoclonal antibody differentially regulates CD11a/CD18 binding to intercellular adhesion molecules CD54, CD102 and CD50

We have made a monoclonal anti-CD44 antibody which is able to activate the leukocyte integrin CD11a/CD18. Activated T cells strongly aggregated, and the aggregation was shown to be intercellular adhesion molecule (ICAM)-1 (CD54) and ICAM-2 (CD102) dependent. Using purified ICAM coated on plastic, only binding to ICAM-1 was increased by the CD44 antibody, whereas activation by phorbol ester increased binding to both ICAM-1 and ICAM-3. The binding to ICAM-2 was not affected by either treatment. These findings show that the CD11a/CD18 integrin can be activated in a ligand-specific manner by engagement of CD44.     

In vivo and in vitro repertoire of CD3+CD4 CD8 thymocytes

CD4-CD8- thymocytes contain a cell subset which expresses thecomplete CD3-TCR complex (/ or /) of which the ontogeny andfiliation are unknown. One of the questions is whether thispopulation can be intrathymically selected, an obligatory stepfor the mature CD4⁺ and CD8⁺ cell differentiation pathway, orif the absence of CD4 and CD8 allows them to escape thymic selection.The repertoire of CD3 ⁺ CD4 - CD8 - (CD3 ⁺ DN) thymocytes wasanalyzed in different strains of mice with different combinationsof H-2 and Mls expression. The expression of V_ß8.1in freshly isolated CD3⁺ DN cells is the highest in Mls-l^b miceand the lowest in MIS-l^a and F₁ mice, suggesting that selectionagainst this specificity can be achieved in vivo. By contrast,a low percentage of V_ß6⁺ cells is found in all thestrains, with no correlation according to MIS expression. Invitro culture of DN thymocytes with IL-1 and IL-2 leads to theproliferation of CD3⁺ DN cells. In vitro culture amplifies thein vivo pattern of V_ß8.1 expression, while V_ß6⁺cells only expand in DN cells of 66 and 61002 Mls-l^b mice withthe same genetic background. These results show: (i) CD3⁺ DNthymic cells can be intrathymically selected but the repertoireis different from that of mature T cells; (ii) V_ß6and V_ß8.1 selection do not follow the same pattern;(iii) this repertoire can be modified by In vitro culture, towarda more mature type; and (iv) comparison of DN cell repertoireof BALBlc, BALB.D2 (congenic for MLs), and other strains ofmice suggests a multigenic control for this selection, and aninvolvement of background genes.     

The role of CD40 and CD154/CD40L in dendritic cells

In this review, we focus on the function of CD40–CD40L (CD154) interactions in the regulation of dendritic cell (DC)–T cell and DC–B cell crosstalk. In addition, we examine differences and similarities between the CD40 signaling pathway in DCs and other innate immune cell receptors, and how these pathways integrate DC functions. As research into DC vaccines and immunotherapies progresses, further understanding of CD40 and DC function will advance the applicability of DCs in immunotherapy for human diseases.