PD-1在弥漫性大B细胞淋巴瘤患者外周血CD4~+T细胞和CD8~+T细胞上的表达和临床意义

目的探讨PD-1在弥漫性大B细胞淋巴瘤外周血CD4+T细胞和CD8+T细胞上的表达及临床意义。方法以32例DLBCL患者为研究对象,同期健康志愿者18例为对照组。应用流式细胞技术比较2组CD4+T细胞和CD8+T细胞PD-1的表达水平的差异,分析CD4+T细胞和CD8+T细胞的PD-1表达与DLBCL患者各临床病理因素的相关性。结果外周血CD4+T细胞和CD8+T细胞的PD-1表达水平在DLBCL组均显著高于对照组,2组间差异有统计学意义(P0.01)。在DLBCL组中,Ann Arbor分期Ⅰ期~Ⅱ期患者CD4+T细胞和CD8+T细胞的PD-1表达水平均低于Ⅲ期~Ⅳ期患者,差异亦有统计学意义(P0.05)。5例DLBCL患者在化疗期间PD-1在CD4+T细胞和CD8+T细胞的表达水平较化疗前有下降趋势。结论 DLBCL患者外周血PD-1表达水平升高,与临床分期和治疗存在一定的相关性。     

乙型肝炎病毒感染患者外周血细胞因子表达分析

目的探讨乙型肝炎病毒(HBV)感染患者外周血中特异性白细胞介素-21(IL-21)+CD_4~+T细胞及γ-干扰素(IFN-γ)+CD8+T细胞表达差异,为阐明HBV感染后T细胞功能衰竭机制提供理论依据。方法选取2013年4月-2015年4月医院收治的HBV感染患者127例,其中慢性乙型肝炎患者41例、非活动性HBsAg携带患者38例、急性乙型肝炎(AHB)患者31例、慢性HBV携带患者17例,再选择同期医院健康体检人员30名作为对照组,比较各组受试者外周血中特异性IL-21+CD_4~+T细胞及IFN-γ+CD8+T细胞表达情况;采用SPSS22.0软件对数据进行统计分析。结果各组受试者特异性IL-21+CD_4~+T细胞比例及非特异性IL-21+CD_4~+T细胞比例均显著高于阴性对照(P0.05),急性乙型肝炎患者特异性IL-21+CD_4~+T细胞比例及非特异性IL-21+CD_4~+T细胞比例较对照组、慢性乙型肝炎、非活动性HBsAg携带、慢性HBV携带显著升高(P0.05);各组受试者特异性IFN-γ+CD8+T细胞比例及非特异性IFN-γ+CD8+T细胞比例均显著高于阴性对照(P0.05),急性乙型肝炎特异性IFN-γ+CD8+T细胞比例及非特异性IFN-γ+CD8+T细胞比例显著高于对照组、慢性乙型肝炎、非活动性HBsAg携带以及慢性HBV携带患者(P0.05);特异性IL-21+CD_4~+T细胞与IFN-γ+CD8+T细胞比例在对照组及各HBV感染组中均呈显著正相关关系(P0.05)。结论在急性乙型肝炎患者中,特异性及非特异性IL-21+CD_4~+T细胞与IFN-γ+CD8+T细胞水平较慢性HBV感染患者显著升高,且特异性IL-21+CD_4~+T细胞与IFN-γ+CD8+T细胞具有着明显的相关性,提示HBV慢性感染患者存在T细胞免疫功能的低下。     

HCV治疗中PD-1/PD-L1信号免疫调控作用的研究概况

丙型肝炎病毒（hepatitis C virus,HCV）感染以其高慢性化、高肝纤维化和高肝细胞癌发生率,已经成为一个全球性的公共卫生问题。本综述拟概述HCV感染和治疗、PD-1（programmed cell death 1 gene,PD-1）高表达与免疫应答在HCV感染中的关联。在抗-HCV治疗中,提高免疫细胞调控能力是决定治疗效果的关键因素之一。慢性HCV感染中,有功能障碍的HCV特异性CD8+ T细胞上PD-1表达水平升高,阻断PD-1/PD-L1（programmed death-ligand 1,PD-L1）信号后,T细胞调控功能部分恢复;PD-1/PD-L1信号的增强,不仅抑制细胞毒性T细胞的功能,还影响CD8+T细胞的分化。临床上,阻断PD-1/PD-L1信号通路后,抗-HCV免疫应答水平增强。因此,加强对HCV感染诱导PD-1高表达的机制和HCV特异性T细胞功能障碍发生的机制研究,将有助于促进慢性HCV感染的预防性和治疗性疫苗的研发,并最终改善HCV治疗的效果。     

免疫检查点分子在妊娠期糖尿病患者调节性T细胞中的表达

目的探讨正常妊娠妇女和妊娠期糖尿病(GDM)患者外周血和脐血调节性T细胞(Treg)免疫检测点分子表达水平。方法流式细胞术检测58例正常妊娠妇女和43例GDM患者外周血和脐血中程序化细胞死亡受体-1(PD-1)、糖皮质激素诱导的肿瘤坏死因子受体(GITR)、人白细胞抗原G(HLA-G)和细胞毒性T淋巴细胞抗原4(CTLA-4)在调节性T细胞(CD4^+Treg细胞和CD8^+Treg细胞)中的表达和调节性T细胞比例。结果与正常妊娠妇女相比,GDM患者外周血和脐血中CD4^+Treg细胞比例降低,CD8^+Treg细胞比例升高,外周血中PD-1和GITR+Treg细胞及脐血中PD-1/CD4^+Treg细胞比例降低,差异均有统计学意义(均P<0.01)。两组中,脐血HLA-G表达高于外周血,而PD-1和GITR表达低于外周血,差异均有统计学意义(均P<0.01)。结论外周血和脐血CD4^+Treg细胞、CD8^+Treg细胞表型及功能具有不同的免疫学特征,PD-1和GITR表达下调可能与GDM有关。     

CD4~+和CD8~+T细胞在HCV感染中免疫应答的差异

CD4~+、CD8~+T细胞在HCV的清除和发病机制中的作用仍不十分清楚,本文作者对HCV感染后病毒学和临床转归不同的丙型肝炎患者,其病毒特异性CD4~+、CD8~+T细胞免疫应答的效力和表现型进行了研究。 作者将研究对象分成3组:第1组为慢     

CD~+T细胞及Treg细胞PD-1表达水平与感染性休克预后的关系

目的分析外周血CD~+T细胞及调节性T细胞(Treg)程序性死亡分子-1(PD-1)表达水平与感染性休克患者预后的关系。方法回顾性分析武汉市肺科医院2015年6月-2019年6月收治的87例患者(感染性休克组)及50名健康体检人群(对照组)的临床资料,比较两组外周血中CD~+T细胞及Treg细胞PD-1表达水平;根据感染性休克患者28 d内存活情况分为存活组和病死组,比较两组CD~+T细胞及Treg细胞PD-1表达水平,并利用受试者工作特征曲线(ROC)分析CD_4~+/CD_8~+及Treg细胞PD-1水平预测感染性休克患者预后的价值,Kaplan-Meier法比较CD_4~+/CD_8~+及Treg细胞PD-1水平与患者的28 d生存率的关系。结果感染性休克患者外周血中CD_3~+、CD_3~+CD_4~+、CD_4~+/CD_8~+水平低于对照组(P0.001),PD-1表达水平高于对照组(P0.001);存活组患者外周血中CD_3~+、CD_3~+CD_4~+、CD_4~+/CD_8~+水平高于病死组(P0.001),PD-1表达水平低于病死组(P0.05);ROC结果显示:CD_4~+/CD_8~+及PD-1表达水平预测患者28 d预后的曲线下面积分别为0.786、0.824,95%CI分别为0.689～0.884、0.725～0.923,截断值分别为0.990、19.880%;Kaplan-Meier分析结果显示:高CD_4~+/CD_8~+患者28 d生存率76.47%(26/34)高于低CD_4~+/CD_8~+患者41.51%(22/53)(P0.001);低Treg PD-1患者28 d生存率75.00%(36/48)高于高Treg PD-1患者30.77%(12/39)(P0.001)。结论感染性休克患者细胞免疫功能降低,而Treg上PD-1会抑制T淋巴细胞水平和免疫功能,因此CD_4~+/CD_8~+、Treg细胞PD-1对感染性休克患者的28 d预后有一定的预测价值。     

CD8~+T淋巴细胞非溶细胞功能抑制HepG2.2.15细胞表达HBV的实验研究

目的 观察慢性乙肝患者病毒特异性CD8+T细胞体外非溶细胞功能抑制HepG2.2.15细胞表达乙型肝炎病毒的作用.方法 选择低溶细胞活性的HBcAg肽特异性CD8+T细胞克隆(效应细胞)与HepG2.2.15细胞(靶细胞)以1:10共同培养,于24 h、48 h和72 h收集培养上清,通过检测其中细胞因子及HBV产物的变化,观察CD8+T克隆对HBV的抑制作用.用抗体中和法观察CD8+T细胞分泌的细胞因子被封闭后HBV抑制的变化.结果 HBV特异性CD8+T克隆与靶细胞共育后,培养上清可检出高水平IFN-γ和少量TNF-α.共育后对HBsAg、HBeAg和HBV-DNA的最高抑制率分别为71.2%、68.5%和78.3%,均在72 h.IFN-γ和TNF-α单独和同时被抗体封闭后,对HBV-DNA的抑制率显著下降.对靶细胞的最大细胞毒活性是7.2%(24 h).结论 IFN-γ和TNF-α是CD8+T细胞非溶细胞机制清除病毒的主要效应分子.     

CD4~+ CD25~+调节性T细胞在HIV/AIDS患者中的作用及其与HIV病毒载量的相关性研究

目的研究HIV感染者/AIDS患者外周血CD4~+CD25~+调节性T细胞(CD4~+CD25~+ regulatory T cell,Treg)频率、功能及其临床意义。方法选择31例HIV感染者/AIDS患者和30例健康对照者,采用流式细胞仪检测各组外周血Treg的表型和频率。采取MACS磁珠分选Treg,利用[~3H]胸腺嘧啶掺入法检测Treg在特异性HIV抗原刺激下对CD4~+CD25~+T细胞的增殖影响。结果HIV/AIDS患者组与正常对照组相比较,外周血CD4~+CD25~+调节性T细胞在统计学上无显著性意义。与正常对照组比较,HIV感染者外周血Treg比例升高,差异有统计学意义(P<0.01);与正常对照组比较,AIDS患者外周血Treg比例降低,差异有统计学意义(P<0.0001)。HIV RNA病毒载量与患者外周血Treg细胞数量呈正相关性(P<0.01)。Treg具有抑制HIV特异性的CD4~+CD25~- T细胞的增殖作用。结论HIV感染者/AIDS患者的细胞免疫功能紊乱,Treg能抑制HIV感染者/AIDS患者的HIV特异性细胞免疫反应,促进HIV病毒复制,与形成持续HIV感染有关。     

婴儿巨细胞病毒肝炎年龄分布及淋巴细胞免疫功能的变化

目的研究婴儿巨细胞病毒(CMV)肝炎淋巴细胞免疫功能变化与年龄分布特点。方法流式细胞术检测110例婴儿CMV肝炎患者及55例健康同龄儿外周血T淋巴细胞亚群(CD3/CD4/CD8)、B淋巴细胞(CD19)、NK细胞(CD16+56)的百分率,两组结果进行比较。并对婴儿CMV肝炎患者年龄进行统计。结果 CMV肝炎年龄1月婴儿占25%,2月婴儿占50%,3月婴儿占15%;巨细胞病毒肝炎与健康对照组相比,CD4+及CD4+/CD8+比值明显下降(P0.01、P0.001),CD8+细胞明显升高(P0.001),较对照组差异有统计学意义,CD3+、CD19+及CD16+56+细胞结果两组间比较差异无统计学意义(P0.05)。结论婴儿CMV肝炎感染与年龄相关,绝大多数在出生后1~3月,患儿细胞免疫功能受损,辅助性T细胞功能低下,抑制性T细胞功能亢进。CD4+、CD8+及CD4+/CD8+比值结果明显异常,T细胞亚群检测可以作为婴儿CMV肝炎的辅助诊断指标。婴幼儿出生后1~3月对巨细胞病毒感染的预防应得到足够重视。     

POI患者雌激素水平与外周血T淋巴细胞亚群及PD-1的相关性

目的 探讨早发性卵巢功能不全(POI)患者雌激素水平与外周血T淋巴细胞亚群及程序性死亡受体1(PD-1)表达量的相关性.方法 选取2019年12月至2021年1月就诊于山西省妇幼保健院门诊的POI患者20例为研究组,选取同期孕前健康体检妇女30例为对照组,所有研究对象的年龄为28～40岁.采用流式细胞术检测20例POI患者和30例健康体检妇女外周血中CD4+、CD8+T淋巴细胞,以及CD4+、CD8+T淋巴细胞表面PD-1的表达;分析PO I患者外周血CD4+、CD8+T淋巴细胞百分比及其PD-1表达量与雌二醇(E2)、抗缪勒管激素(AMH)、促甲状腺激素(TSH)水平的相关性.结果 研究组CD4+T淋巴细胞百分比低于对照组(t=4.919,P<0.05),而CD8+T淋巴细胞百分比高于对照组(t=-3.865,P<0.05);研究组的CD4+PD-1+和CD8+PD-1+表达量均显著低于对照组(t值分别为4.156、5.400,P<0.05).POI患者血清E2水平与CD4+T淋巴细胞百分比呈正相关(r=0.530,P<0.05);血清E2水平与CD4+PD-1+和CD8+PD-1+表达量均呈正相关(r分别为0.415、0.437,P<0.05).POI患者血清AM H水平与CD4+T淋巴细胞百分比呈正相关(r=0.504,P<0.05),与CD8+T淋巴细胞百分比呈负相关(r=-0.430,P<0.05);血清A M H水平与CD4+PD-1+和CD8+PD-1+表达量均呈正相关(r分别为0.415、0.649,P<0.05).PO I患者血清T S H水平与CD4+T淋巴细胞百分比呈负相关(r=-0.400,P<0.05),与CD8+T淋巴细胞百分比呈正相关(r=0.467,P<0.05);血清TSH水平与CD4+PD-1+和CD8+PD-1+表达量均呈负相关(r分别为-0.340、-0.352,P<0.05).结论 PO I患者细胞免疫水平降低与E2水平相关.     

PD-1/PD-L负性协同刺激途径与慢性病毒感染

PD-1(programmed death 1)是用消减杂交技术从发生程序性死亡的T细胞株中分离得到的一种跨膜蛋白,是一种负向协同刺激分子。PD-1及其配体PD-L所介导的信号在维持机体自身免疫耐受中具有重要意义,最新研究发现该途径与宿主的病毒感染慢性化密切相关。此文在论述PD-1及其配体PD-L的基本结构、表达和生物学功能的基础上,进一步就其与病毒感染的关系、作用及其在抗慢性病毒感染治疗中应用的潜在前景予以综述。     

LAH4 enhances CD8+ T cell immunity of protein/peptide-based vaccines

It is now clear that CD8+ T cells are crucial for therapeutic immunity against chronic viral infections and/or tumors. We reason that a strategy capable of improving CD8+ T cell activation would improve the efficacy of protein-based vaccines, which predominantly generate CD4+ T cell-mediated responses. Herein, we explore the ability of a novel cell-penetrating peptide (CPP), LAH4, to facilitate intracellular delivery of protein-based vaccines adjuvanted with Toll-like receptor 9 agonist CpG oligonucleotide (CpG) to generate enhanced CD8+ T cell immune responses and antitumor effects. LAH4 was found to mediate the intracellular delivery of both protein and nucleotide cargo and facilitate protein internalization using mechanisms involving endosomal acidification and processing through the proteasome pathway, leading to enhanced cross presentation of protein antigen by dendritic cells to CD8+ T cells. LAH4 also improved the internalization of CpG, resulting in NFkB activation, thus potentiating the adjuvant effect of CpG. We found that protein-based vaccine comprised of LAH4 mixed with model antigen and CpG generated significantly improved antigen-specific CD8+ T cell immune responses and/or antitumor effects. Furthermore, we found that LAH4 was able to enhance the ability of a tyrosinase-related protein 2 (TRP-2) peptide-based vaccine to generate TRP2-specific CD8+ T cells and antitumor effects against TRP2-expressing tumors. Thus, our results suggest that CPP technology using LAH4 is able to enhance both protein-based and peptide-based vaccine potency to generate antigen-specific CD8+ T cells and antitumor effects. Our findings serve as an important foundation for future clinical applications of CPP technology to improve protein/peptide-based vaccine potency.     

Enhancement of T cell-mediated immune responses to whole inactivated influenza virus by chloroquine treatment in vivo

Current influenza vaccines induce poor cross-reactive CD8+ T cell responses. Cellular immunity is generally specific for epitopes that are remarkably conserved among different subtypes, suggesting that strategies to improve the cross-presentation of viral antigens by dendritic cells (DC) could elicit a broadly protective immune response. Previous studies have shown that limited proteolysis within the endocytic pathway can favorably influence antigen processing and thus immune responses. Herein, we demonstrate that chloroquine improves the cross-presentation of non-replicating influenza virus in vitro and T cell responses in mice following a single administration of inactivated HI-X31 virus. CD8+ T cells were also recruited to lymph nodes draining the site of infection and able to reduce viral load following pulmonary challenge with the heterologous PR8 virus. These findings may have implications for vaccination strategies aimed at improving the cross-presentation capacity of DCs and thus the size of effector and memory CD8+ T cells against influenza vaccines.     

Galectin-9/T细胞免疫球蛋白黏蛋白分子3信号通路在抗感染免疫中的作用

T细胞免疫球蛋白黏蛋白分子3(Tim-3)在CD4、CD8、NK细胞中主要发挥免疫抑制作用.研究显示,在HIV感染者、乙型和丙型肝炎患者、活动性结核病患者外周血及病变局部T细胞或NK细胞中,Tim-3表达均显著增高,而且与疾病的发生和发展密切相关.阻断Tim-3信号通路可以显著提高T细胞、NK细胞功能,并有望用于这些疾...     

Induction of cytotoxic T lymphocyte responses against hepatitis delta virus antigens which protect against tumor formation in mice

The cellular immune response is a crucial defense mechanism against hepatotropic viruses and in chronic viral hepatitis prevention. Moreover, hepatitis delta virus (HDV) immunogenicity may be an important component in the development of prophylactic and therapeutic vaccines. Therefore, we evaluated the immunogenicity of the small (HDAg) or large delta antigen (LHDAg) to be used as a DNA-based vaccine. We immunized different mouse haplotypes, determined cellular immune responses, and tested protection of animals against tumor formation using syngeneic tumor cells stably expressing the delta antigens. Both LHDAg and HDAg primed CD4+ and CD8+ T cell immunity against both forms of delta antigens. CD8+ T cell frequencies were about 1% and antigen-specific CD8+ T cells remained detectable directly ex vivo for at least 35 days post-injection. No anti-delta antibody responses could be detected despite multiple detection systems and varied immunization approaches. We observed protection against syngeneic tumor formation and growth in mice immunized with DNA plasmids encoding secreted or intracellular forms of HDAg and LHDAg but not with recombinant HDAg establishing the generation of significant cellular immunity in vivo. Both CD4+ and CD8+ T cells were required for antitumoral activity as determined by in vivo T cell depletion experiments. The results indicate that DNA-based immunization with genes encoding LHDAg and HDAg induces strong T cell responses and, therefore, is an attractive approach for the construction of therapeutic and prophylactic T cell vaccines against HDV.     

HIV-1感染者CD8+T细胞受体基因多样性特点及其与病毒载量的相关性

目的 研究HIV-1感染者CD8+T细胞受体(TCR)基因的多样性变化特征及其与病毒载量的相关性.方法 应用抗CD8单克隆抗体从9份HIV-1感染者和7份HIV-1阴性对照样本外周血单个核细胞中分离CD8+T细胞,提取总RNA,然后采用一步(one step)及巢式(nested)多聚酶链式反应(PCR)的方法对22个T细胞受体Vβ基因家族的瓦补决定区3(CDR3)进行扩增,利用ABI-3700测序仪对扩增的PCR产物进行扣描,定量分析HIV-1感染者TCR CDR3区多样性变化特征及其与病毒载量的相关性.结果 HIV-1感染者和正常人相比较其CD8+T细胞的TCR基因多样性明显减少,部分TCR Vβ基因家族CDR3区的高斯分布破坏;TCR的紊乱与病毒载量呈正相关(r=0.771,P<0.05);HIV-1感染引起患者TCR多样性的改变不仅表现在不同Vβ基因家族上,而且也表现在CDR3长度上,其中感染者VB2、Vβ4、Vβ5、Vβ17、Vβ20、Vβ21、Vβ23及Vβ24基因家族的变化与正常人存在统计学差异.结论 HIV-1感染能引起CD8+T细胞TCR基因多样性的减少及高斯分布的破坏,TCR CDR3区的紊乱与病毒载量呈正相关.     

The absence of correlation between immunoregulatory T cells and induced lymphoproliferative response in treated B-chronic lymphocytic leukemia patients.

BACKGROUND: Many data suggest T cell functional impairment in B-cell chronic lymphocytic leukemia (B-CLL). The mechanism responsible for this phenomenon is still unresolved. METHODS: In 88 B-CLL patients (RAI II-IV) the relationship between immunoregulatory T cells and PHA induced lymphoproliferative response (LPR) was analysed before and after the therapy. The number of peripheral blood CD3+, CD4+ and CD8+ T lymphocytes was determined by indirect immunofluorescence assay using monoclonal antibodies. LPR was estimated in whole blood culture method. RESULTS: The absolute number of CD3+, CD4+ and CD8+ cells in untreated CLL patients was much higher than in healthy controls (n = 26), but the percentages of these subpopulations, CD4/CD8 ratio and LPR to PHA were significantly (p < 0.00001) decreased. The chemotherapy induced a significant rise of CD3+ and CD4+ percentages (p < 0.006 < p < 0.022 respectively) in comparison to baseline levels, but their levels remained significantly (p < 0.00001) lower than the controls. The CD4/CD8 ratio was also elevated after the therapy (p < 0.048) but remained below the normal value as well. The absolute number of CD3+ and CD4+ T cells were normalized after treatment, while the CD8+ cells were still higher (p < 0.044) than controls. The increase of LPR has been registered after treatment, but it failed to reach the control values. We could not find any correlation between the number of immunoregulatory T cells and induced LPR (r = 0.07, for CD4+; r = 0.09 for CD8+ cells). CONCLUSIONS: These data indicate some profound lymphoid cell defect in CLL patients affecting CD8+ proliferation as well as LPR.     

Single CX3CL1-Ig DNA administration enhances T cell priming in vivo

Upon antigenic stimulation, establishment of adaptive immune responses that determines vaccine efficacy is dependent on efficient T cell priming. Here, single CX3CL1-Ig DNA administration, a unique ligand of CX3CR1, together with viral or tumor antigens induced a strong in vivo antigen-specific T cell proliferation and effector function that was enough efficient to protect against a tumor challenge. We also showed that early expression of CX3CL1-Ig and antigens in muscle and lymphoid organs induces an increased in vivo migration of myeloid CD14+CD11c+ DC but not lymphoid CD8alpha+CD11c+ DC at these sites. Thus, by effectively directing DC toward lymphoid organs to encounter T cells, CX3CL1-Ig become a new candidate that augments T cell priming and increases efficiency of vaccination.     

Analyse der Immunantwort bei Hepatitis C

The outcome of Hepatitis C virus infection depends on the interaction of the hosts immune system, particularly the virus specific T cell response, with the virus. An early vigorous multispecific TH1 lymphokine dominated and persistant CD4+ and CD8+ T cell response is associated with elimination (control) of the virus and self limited acute hepatitis C, whereas an absent or weak T cell response is associated with viral persistence and chronic course of disease. The weak immune response during chronic hepatitis C is insufficient to eradicate the virus, at best it may exert a certain control but on the other hand contributes to chronic liver damage. The role of the humoral immune response is not clearly defined yet. Understanding the HCV specific T cell response is of great importance since it paves the way for novel therapeutic and prophylactic vaccine approaches for this devastating disease.     

Vaccination with human papillomavirus-18 E1 protein plus α-galactosyl-ceramide induces CD8+ cytotoxic response and impairs the growth of E1-expressing tumors

CD8+ T cell-mediated immune response plays a major role in the clearance of virus-infected cells, including human papillomavirus (HPV). The effective treatment of women with normal cytology but persistent high risk-HPV infection or with low-grade intraepithelial lesions could take advantage of novel strategies based on vaccination with viral immunological targets with a wide spectrum of cross-protection. The helicase E1, expressed early during viral replication in HPV infection, is among the most conserved papillomavirus proteins, which makes it a good vaccine candidate. In the present study, we examined E1-specific CD8+ T cell and NK immune responses in a mouse model with α-galactosylceramide (α-GalCer) as an adjuvant. We found that mice immunized with E1 combined with α-GalCer elicited an E1-specific CD8+ T and NK cell cytotoxic responses, which correlated with growth inhibition of grafted melanoma B16-F0 cells expressing E1, both in prophylactic and therapeutic protocols.