HIV-1gag/IFNα-2b表达产物的生物活性研究

目的:将艾滋病病毒核心蛋白(gag)与干扰素(IFNα-2b)融合基因表达的融合蛋白作为免疫原免疫小鼠,动态观察小鼠的体液免疫、细胞免疫与CTL应答.方法:将IFNα-2b基因片段插入到gag基因的nt531位点,经脂质体转染与血凝素阴性蚀斑筛选,挑出重组痘苗病毒.经SDS-PAGE和Western blot鉴定表达产物.以小鼠为实验对象,用重组痘苗病毒vJ38gag/IFNα-2b免疫小鼠,用ELISA方法检测血清IgG抗体含量.用流式细胞仪测定小鼠外周血CD+4、CD+8T淋巴细胞计数.3H-TdR掺入法检测细胞毒性T淋巴细胞杀伤活性.结果:血清IgG抗体含量逐渐增高,实验组与对照组比较差异有显著性意义(p＜0.05).CD+4、CD+8T淋巴细胞计数、CTL检测实验组与对照组比较差异均有显著性意义(p＜0.05).结论:重组痘苗病毒vJ38gag/IFNα-2b能增强小鼠的体液免疫、细胞免疫和CTL应答.IFNα-2b可以作为免疫佐剂增强机体的免疫状态.     

HIV—lgag／IFNα—2b表达产物的生物活性研究

目的 :将艾滋病病毒核心蛋白 (gag)与干扰素 (IFNα - 2b)融合基因表达的融合蛋白作为免疫原免疫小鼠 ,动态观察小鼠的体液免疫、细胞免疫与CTL应答。方法 :将IFNα - 2b基因片段插入到gag基因的nt5 31位点 ,经脂质体转染与血凝素阴性蚀斑筛选 ,挑出重组痘苗病毒。经SDS -PAGE和Westernblot鉴定表达产物。以小鼠为实验对象 ,用重组痘苗病毒vJ38gag/IFNα - 2b免疫小鼠 ,用ELISA方法检测血清IgG抗体含量。用流式细胞仪测定小鼠外周血CD 4 、CD 8T淋巴细胞计数。 3H -TdR掺入法检测细胞毒性T淋巴细胞杀伤活性。结果 :血清IgG抗体含量逐渐增高 ,实验组与对照组比较差异有显著性意义 (p <0 .0 5 )。CD 4 、CD 8T淋巴细胞计数、CTL检测实验组与对照组比较差异均有显著性意义 (p <0 .0 5 )。结论 :重组痘苗病毒vJ38gag/IFNα - 2b能增强小鼠的体液免疫、细胞免疫和CTL应答。IFNα - 2b可以作为免疫佐剂增强机体的免疫状态。     

HIV结构蛋白与痘苗病毒共表达产物的免疫原性研究

目的 将艾滋病病毒外膜蛋白(env)与干扰素(IFNα-2b)融合基因表达的融合蛋白作为免疫原免疫小鼠,观察小鼠的免疫功能状态和细胞免疫应答.方法 将IFNα-2b基因片段插入到env基因的下游,经脂质体转染,筛选重组痘苗病毒,经SDS-PAGE和Western blot鉴定表达产物.用重组病毒vJ1 6env/IFNα-2b免疫小鼠,以生理盐水和野生型痘苗病毒作为对照,检测小鼠脾淋巴细胞对ConA、LPS及IgG的反应性;用流式细胞仪测定小鼠脾淋巴细胞CD4 、CD8T细胞计数与CTL.结果 与对照组比较,实验组脾淋巴细胞对ConA、LPS及IgG的反应性显著增高(P＜0.05);CD4T淋巴细胞计数和CTL活性也显著增高(P＜0.05);CD8T淋巴细胞计数呈增高趋势,但未达到显著意义的程度.结论 重组痘苗病毒v J16env/IFNα-2b能增强小鼠的免疫功能和诱导细胞免疫.     

气温骤降前后慢性阻塞性肺疾病患者免疫情况的变化

目的:探讨COPD患者免疫功能在外界温度变化时的变化.方法:T淋巴细胞亚群测定采用单克隆抗体免疫组化荧光染色法.血清免疫球蛋白(IgG、IgA、IgM)用琼脂单向扩散法.结果:COPD患者体温骤降后CD3、CD4、CD4/CD8明显降低,CD8明显升高,IgG、IgA、IgM降低,与对照组相比有显著性差异(P＜0.01).体温下降前与体温下降后比较差异无统计学意义(P＞0.05).结论:体温骤降致COPD患者细胞免疫和体液免疫功能失衡,体温骤降后较体温骤降前体液免疫及细胞免疫功能进一步降低.     

体液免疫和细胞免疫功能检测对梅毒患者的诊断意义

目的探讨体液免疫和细胞免疫功能检测对梅毒患者的诊断意义。方法收集56例未经驱梅治疗的梅毒患者纳入实验组,同时随机抽取56例行健康体检的志愿者纳入对照组,比较两组受试者体液免疫及细胞免疫指标检测值。结果实验组IgG、IgA、IgM检测值均明显高于对照组(P0.05),一期梅毒患者各项检测值与对照组比较差异无明显统计学意义(P0.05),二期梅毒与潜伏梅毒患者各项检测值均较对照组明显升高(P0.05)。实验组CD3+、CD4+、CD4+/CD8+、NK细胞检测值均明显低于对照组,CD8+细胞检测值明显高于对照组(P0.05),CD8+指标变化以二期梅毒患者较为显著(P0.05)。结论梅毒患者存在体液免疫功能亢进、细胞免疫功能缺陷的特点,行免疫功能检测对梅毒诊断具有一定临床价值。     

肝癌患者体液免疫和细胞免疫的变化情况

目的:探讨肝癌患者体液免疫和细胞免疫功能状况。方法:选取2012年1月20日至2015年3月25日在西宁市第一人民医院就诊的126例肝癌患者和87名健康者作为研究对象,采用免疫透射比浊法测定血清IgA、IgG水平,采用流式细胞术检测外周血T淋巴细胞亚群CD3~+、CD4~+、CD8~+和CD4~+/CD8~+水平。结果:与健康对照组相比,肝癌组患者血清中IgA和IgG水平显著升高(P0.05),外周血中T淋巴细胞亚群CD3~+、CD4~+和CD4~+/CD8~+显著降低(P0.05),CD8~+显著升高(P0.05)。结论:肝癌患者体液免疫功能增强,细胞免疫功能降低,外周血T细胞亚群和血清免疫球蛋白的检测对了解肝癌患者的病情、预后以及免疫治疗具有一定的临床指导意义。     

豫医无毛小鼠分离近交系T细胞亚群和sIL-2R水平

为研究豫医无毛小鼠分离近交系细胞免疫功能,采用单抗致敏的红细胞花环法和双抗夹心ELISA法分别对2月龄、6月龄无毛小鼠及杂合子有毛小鼠T淋巴细胞亚群及可溶性白介素-2受体(sIL-2R)水平进行体外测定,结果表明, 2月龄组无毛小鼠CD3、 CD4、 CD8 阳性T 细胞及CD4/CD8与有毛小鼠相比无显著性差异,sIL-2R水平无毛小鼠高于有毛小鼠,差异显著(P<0.05);6月龄组无毛小鼠与有毛小鼠相比,CD4无显著性差异,CD3、 CD4/CD8高于有毛小鼠,CD8 、sIL-2R低于有毛小鼠,差异显著(P<0.05).提示了豫医无毛小鼠分离近交系两种基因型小鼠细胞免疫功能有一定差异.     

猪白细胞介素2与融合白细胞介素4/6基因共表达的免疫效应研究

目的构建猪融合白细胞介素4/6与猪白细胞介素2基因的共表达载体,研究其共表达对小鼠免疫的协同效应。方法以2A自剪接技术首次构建猪融合白细胞介素4/6与白细胞介素2基因的共表达重组质粒,以壳聚糖纳米材料包裹制成纳米颗粒,进行体外转染HEK293细胞,提取总RNA进行RT-PCR分析,最后肌肉注射小鼠进行体内实验并分析。结果成功构建了重组共表达质粒VRIL4/6-2;壳聚糖包裹后转染HEK293细胞,48 h后收集细胞,RT-PCR检测显示目的基因能够在HEK293细胞中高效地转录与表达。小鼠接种实验结果表明,实验组血清中的IgG和IgG2a的含量比对照组显著增加,并且VRIL4/6-2-CS接种组的小鼠体液免疫水平明显增高(P0.05);VRIL4/6-2实验组的CD4+淋巴细胞显著多于其它实验组(P0.05);实验组IL-2、IL-4、IL-6、IL-23基因的表达水平明显高于对照组(P0.05),实验组小鼠外周血白细胞、血小板和血红蛋白的含量均显著高于对照组(P0.05)。结论 VRIL4/6-2共表达质粒能够更好的增强动物体液免疫和细胞免疫机能,可作为提高动物体液免疫和细胞免疫的经济高效安全新型免疫调节剂,具有潜在的重要应用前景。     

H5N1重组禽流感病毒样颗粒免疫原性研究

目的对构建的H5N1重组禽流感病毒样颗粒(VLPs)进行初步免疫原性探讨,并与H5N1全病毒灭活疫苗(WIV)进行体液免疫和细胞免疫的比较。方法在0周和3周分别以纯化H5N1重组禽流感病毒样颗粒、H5N1全病毒灭活疫苗及pH7.2 PBS腿部肌肉注射BALB/c小鼠,于不同时间收集血清,以血凝抑制试验(HI)和血清IgG抗体酶联免疫吸附试验(ELISA)评估体液免疫,CD4+、CD8+T细胞亚群及酶联免疫斑点试验(ELISPOT)评估细胞免疫,并以同型毒株滴鼻攻击,观察小鼠存活率。结果病毒样颗粒各组和全病毒灭活疫苗免疫后小鼠血清ELISA IgG效价均有升高;中和抗体效价除病毒样颗粒120 ng/只免疫剂量外其他免疫小鼠HI效价均达1︰40;小鼠脾CD4+T淋巴细胞亚群分类:全病毒灭活疫苗组(600μg/只)为36.56%;病毒样颗粒组(120 ng/只,600 ng/只,2 500 ng/只)分别为26.58%,32.20%,29.25%;PBS组为26.65%;CD8+T淋巴细胞亚群分类:全病毒灭活疫苗组(600 ng/只)为10.78%;病毒样颗粒组(120 ng/只,600 ng/只,2 500 ng/只)分别为1 3.53%,14.24%,1 3.35%;PBS组为10.69%。ELISPOT试验统计学数据显示,病毒样颗粒和全病毒灭活疫苗的小鼠脾单个核细胞分泌IFN-γ细胞与PBS组有显著性差异;小鼠保护性试验结果显示,除病毒样颗粒120 ng/只免疫剂量小鼠的存活率为87.5%外,其他病毒样颗粒实验组小鼠均为100%,PBS对照组为12.5%。结论 H5N1重组禽流感病毒样颗粒能诱导体液免疫和细胞免疫,并能抵御同型病毒株的攻击,可作为H5N1人用禽流感的候选疫苗。     

SARS-CoV-2重组S1和S蛋白疫苗诱导保护性免疫的研究*

目的:评价新型冠状病毒(SARS-CoV-2)重组S1蛋白和S蛋白疫苗对SARS-CoV-2的免疫保护效果。方法:将SARS-CoV-2重组S1蛋白和S蛋白分别联合氢氧化铝佐剂以0.1 μg/只、1 μg/只、5 μg/只、10 μg/只不同剂量接种6~8周BALB/c纯系健康雌性小鼠。第二次免疫后采血通过酶联免疫吸附试验(ELISA)检测血清中IgG抗体效价,通过假病毒中和试验比较免疫小鼠血清对SARS-CoV-2野生型株(WT)、英国株(B.1.1.7)、巴西株(P.1)、印度株(B.1.617.2)、Mu毒株(B.1.621)和南非株(501Y.V2-1)六种假病毒毒株中和活性效价,取脾细胞通过酶联免疫斑点技术(ELISpot)检测免疫小鼠的细胞免疫水平。结果:SARS-CoV-2重组S和S1蛋白都能诱导小鼠产生较强的IgG抗体水平。免疫S1蛋白的小鼠血清对SARS-CoV-2野生型株、英国株、巴西株有明显的中和活性,免疫S蛋白的小鼠血清除了对SARS-CoV-2野生型株、英国株、巴西株有明显中和活性之外,对印度株也有明显的中和活性,两种蛋白质免疫的小鼠血清均对野生型株中和效果最强。S蛋白免疫的小鼠脾细胞能够显著诱导出γ干扰素(IFN-γ)和白介素-4(IL-4)的产生。S蛋白诱导产生的IgG抗体、中和抗体、细胞免疫水平均高于S1。结论:SARS-CoV-2重组S蛋白疫苗能够诱导产生较强的保护性免疫应答。     

BALB/c突变无毛小鼠特异性免疫功能的研究

目的　BALB c突变无毛小鼠的皮肤和被毛结构的突变是否影响机体的免疫功能 ,为此研究其免疫功能。方法　通过流式细胞仪和ELISA方法。对特异性免疫指标CD4+ 、CD3+ 、CD8+ 、CD19+ 、IgG进行检测。结果　各项指标雌雄之间差异不显著 ,无毛小鼠的各项指标均低于其他表型的指标。各组之间方差分析结果 :CD8+ 差异显著 ,其他指标差异不显著。IgG抗体的吸光度的结果 ,三种表型之间差异不显著。结论　该小鼠的皮肤和被毛突变对免疫功能有一定的影响。     

Immune status and proinflammatury cytokines in pregnant women with acute cytomegalovirus infection

A total of 64 pregnant women aged 16-40 years with acute cytomegalovirus (CMV) infection were examined. CMV infection was diagnosed by the detection of anti- CMV IgM (by the enzyme immunoassay) or DNA by PCR in the blood. The immunophenotype of lymphocytes CD3+, CD4+, CD8+, CD16+, CD19+, IgG, IgM, IgA and the spontaneous production of TNFalpha and IL-8 in the blood were studied. In pregnant women with CMV infection the presence of the immunosuppression of cell-mediated immunity reactions, the hyperproduction of Fc-receptors of natural killers, B lymphocytes (CD19+), the hyperglobulinemia of serum IgM and IgG, as well as the increased synthesis of proinflammatory cytokines--TNFalpha and IL-8--were established.     

Three different vaccines based on the 140-amino acid MUC1 peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus MUC1-transgenic mice with different potential for tumor rejection

Low-frequency CTL and low-titer IgM responses against tumor-associated Ag MUC1 are present in cancer patients but do not prevent cancer growth. Boosting MUC1-specific immunity with vaccines, especially effector mechanisms responsible for tumor rejection, is an important goal. We studied immunogenicity, tumor rejection potential, and safety of three vaccines: 1) MUC1 peptide admixed with murine GM-CSF as an adjuvant; 2) MUC1 peptide admixed with adjuvant SB-AS2; and 3) MUC1 peptide-pulsed dendritic cells (DC). We examined the qualitative and quantitative differences in humoral and T cell-mediated MUC1-specific immunity elicited in human MUC1-transgenic (Tg) mice compared with wild-type (WT) mice. Adjuvant-based vaccines induced MUC1-specific Abs but failed to stimulate MUC1-specific T cells. MUC1 peptide with GM-CSF induced IgG1 and IgG2b in WT mice but only IgM in MUC1-Tg mice. MUC1 peptide with SB-AS2 induced high-titer IgG1, IgG2b, and IgG3 Abs in both WT and MUC1-Tg mice. Induction of IgG responses was T cell independent and did not have any effect on tumor growth. MUC1 peptide-loaded DC induced only T cell immunity. If injected together with soluble peptide, the DC vaccine also triggered Ab production. Importantly, the DC vaccine elicited tumor rejection responses in both WT and MUC1-Tg mice. These responses correlated with the induction of MUC1-specific CD4+ and CD8+ T cells in WT mice, but only CD8(+) T cells in MUC1-Tg mice. Even though MUC1-specific CD4+ T cell tolerance was not broken, the capacity of MUC1-Tg mice to reject tumor was not compromised.     

Regulatory function for murine intraepithelial lymphocytes. Two subsets of CD3+, T cell receptor-1+ intraepithelial lymphocyte T cells abrogate oral tolerance

The murine intraepithelial lymphocyte (IEL) population is enriched in T cells that express the gamma delta-TCR, however, the biologic function served by these T cells remains obscure. IEL are considered to be major effector cells in mucosal immunity, and we have investigated whether IEL subsets could reverse orally induced systemic unresponsiveness (oral tolerance; OT) and support secondary type responses when adoptively transferred to mice orally tolerized with SRBC. When purified CD3+ IEL from mice orally primed with SRBC were transferred to adoptive hosts and challenged with SRBC, splenic IgM, IgG1, IgG2b, and IgA anti-SRBC plaque-forming cell responses were observed. However, CD3+ IEL from HRBC orally primed mice did not abrogate SRBC induced OT. Further, HRBC-primed CD3+, IEL converted HRBC-specific OT but not SRBC-specific OT. CD3+ IEL could be separated into four subsets based on expression of CD4 and CD8. CD3+, CD4-, 8+ T cells were the major subset (74.5%), with smaller numbers of CD4- and CD8- (double negatives, DN) (7.8%), CD4+, 8- (7.6%) and CD4+, CD8+ (double positives) (10.1%) T cells. Interestingly, both the CD3+, CD8+, and the CD3+, DN IEL subsets abrogated OT, resulting in significant IgM, IgG1, IgG2b, and IgA anti-SRBC plaque-forming cell responses when adoptively transferred to mice with OT. However, neither CD3+, CD4+, CD8-, nor double positive T cells affected OT when studied in this system. The CD3+, CD8+ IEL subset could be further separated into Thy-1+ (16.6%) and Thy-1- (83.4%) cells; adoptive transfer of Thy-1- cells abrogated oral tolerance whereas the Thy-1+ subset was without effect. When the expression of TCR on IEL with this biologic function was determined by use of monoclonal anti-alpha beta TCR (H57.597), TCR2-, CD3+ IEL possessed immunoregulatory function whereas the alpha beta-TCR+ (TCR2+) fraction did not abrogate OT. Immunoprecipitation of membrane fractions obtained from purified CD3+, CD4-, CD8+, Thy-1- IEL with polyclonal anti-delta peptide (Tyr-Ala-Asn-Ser-Phe-Asn-Asn-Glu-Lys-Leu) antibody revealed bands of 45 and 35 kDa, corresponding to the delta- and gamma-chains, respectively. These results suggest that gamma delta-TCR+ IEL possess a regulatory function, namely the restoration of immune responses in a state of oral tolerance. Further, both CD3+, CD4-, CD8+, Thy-1-, and CD3+, DN IEL T cells exhibit this effector contrasuppressor function.     

Distinct effects of TGF-beta 1 on CD4+ and CD8+ T cell survival, division, and IL-2 production: a role for T cell intrinsic Smad3

TGF-beta1 is critical for maintaining T cell homeostasis. Smad3 has been implicated in this regulatory process, yet the cellular targets and molecular details remain poorly understood. In this study, we report that TGF-beta1 impairs the entry of CD4+ and CD8+ T cells into the cell cycle as well as their progression through subsequent rounds of division, and show that Smad3 is essential for TGF-beta1 to inhibit TCR-induced division of only CD4+ and not CD8+ T cells. Both CD8+ and CD4+ T cells from Smad3-/- mice were refractory to TGF-beta1-induced inhibition of IL-2 production, thus demonstrating that not all CD8+ T cell responses to TGF-beta1 are Smad3 independent. These TGF-beta1 effects were all T cell intrinsic, as they were reproduced in purified CD4+ and CD8+ T cells. Finally, we found that Smad3 was critical for the survival of CD8+, but not CD4+ T cells following activation ex vivo. The TCR-induced death of Smad3-/- CD8+ T cells was not dependent upon TNF-alpha production. Exogenous TGF-beta1 partially rescued the CD8+ T cells by signaling through a Smad3-independent pathway. TGF-beta1 also enhanced survival of TCR-stimulated CD4+CD44high T cells in a Smad3-independent manner. Collectively, these findings firmly establish for the first time that TGF-beta1 discriminately regulates CD4+ and CD8+ T cell expansion by signaling through distinct intracellular pathways.     

Partial protection of mice against Trypanosoma cruzi after immunizing with the TcY 72 antigenic preparation

A 72 kDa Trypanosoma cruzi glycoprotein recognized by the 164C11 monoclonal antibody (IgM isotype) was purified by preparative electrophoresis. The antigenic preparation obtained, named TcY 72, was used to immunize C57Bl/10 mice. The following results were observed after immunization: (1) induction of higher titres of IgG than IgM antibodies, as evaluated by indirect immunofluorescence; (2) significant DTH after injection of epimastigotes in mice footpads; (3) peak parasitemia in immunized mice was significantly reduced and animals were negative by 13 days post-infection, although the mice still succumb to infection; (4) the phenotypic analysis of spleen cell populations showed a decrease in the CD4/CD8 ratio in immunized mice. Taken as a whole, these findings indicate that TcY 72 is immunogenic and potentially important for protective immunity.     

A standardized root extract of Withania somnifera and its major constituent withanolide-A elicit humoral and cell-mediated immune responses by up regulation of Th1-dominant polarization in BALB/c mice

The effects of graded doses of a chemically standardized aqueous alcoholic (1:1) root extract (AGB) of Withania somnifera on the immune system of SRBC immunized BALB/c mice were investigated. Mice were administrated AGB orally for 15 days. AGB stimulated cell mediated immunity, IgM and IgG titers reaching peak value with 30 mg/kg b.wt. Flow cytometric analysis of lymphocyte surface markers of T cells (CD3(+), CD4(+) and CD8(+)) and B cells (CD19(+)) indicated prominent enhancement in proliferation and differentiation of lymphocytes. The extract selectively, induced type 1 immunity because it guided enhanced expression of T helper cells (Th)1 cytokines interferon (IFN)-gamma and interleukin (IL)-2 while Th2 cytokine IL-4 observed a moderate decline. Confirmation of Th1 polarization was obtained from augmented levels of IgG2a over IgG1 in the blood sera of AGB treated groups. Withanolide-A, a major constituent of AGB appeared responsible for Th1 skewing effect of the extract as it significantly increased the levels of Th1 cytokines, decreased moderately IL-4 and significantly restored the selective dexamethasone inhibition of Th1 cytokines in mouse splenocytes cultures in vitro. In addition, AGB also strongly activated macrophage functions ex vivo and in vitro indicated by enhanced secretion of nitrite, IL-12 and TNF-alpha. In contrast IL-10 remained unchanged again suggesting that AGB critically influenced Th1 profile of the cytokines. The studies suggested that AGB supports predominantly Th1 immunity with increase in macrophage functions. The standardized root extract of no toxicological consequences might therefore, find useful applications against the intracellular pathogens and in the management of immune suppressed diseases.     

TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling

We recently reported that TNFR-associated factor (TRAF)3, a ubiquitously expressed adaptor protein, promotes mature B cell apoptosis. However, the specific function of TRAF3 in T cells has remained unclear. In this article, we report the generation and characterization of T cell-specific TRAF3(-/-) mice, in which the traf3 gene was deleted from thymocytes and T cells. Ablation of TRAF3 in the T cell lineage did not affect CD4 or CD8 T cell populations in secondary lymphoid organs or the numbers or proportions of CD4(+),CD8(+) or double-positive or double-negative thymocytes, except that the T cell-specific TRAF3(-/-) mice had a 2-fold increase in FoxP3(+) T cells. In striking contrast to mice lacking TRAF3 in B cells, the T cell TRAF3-deficient mice exhibited defective IgG1 responses to a T-dependent Ag, as well as impaired T cell-mediated immunity to infection with Listeria monocytogenes. Surprisingly, we found that TRAF3 was recruited to the TCR/CD28 signaling complex upon costimulation and that TCR/CD28-mediated proximal and distal signaling events were compromised by TRAF3 deficiency. These findings provide insights into the roles played by TRAF3 in T cell activation and T cell-mediated immunity.     

TCR vaccines against a murine T cell lymphoma: a primary role for antibodies of the IgG2c class in tumor protection

Tumor-associated proteins can act as effective immunotherapeutic targets. Immunization with tumor TCR protein conjugated to the immunogenic protein keyhole limpet hemocyanin (KLH) protects mice from tumor challenge with the murine T cell lymphoma C6VL. The immune mechanisms responsible for this tumor protection are of interest for designing more effective vaccine strategies. Previous studies using depletion experiments had suggested a CD8-mediated component of protection induced by TCR-KLH vaccines. In this study we used CD8alpha knockout, micro MT, and FcgammaR knockout mice to investigate the relative roles of CD8+ T cells and Ab in protective immunity induced by TCR-KLH immunization. We found that CD8+ T cells are not required for tumor protection, although they may contribute to protection. Vaccine-induced Abs are sufficient to mediate protection against this murine T cell lymphoma through an FcR-dependent mechanism. This was confirmed with Ab transfers, which protect challenged mice. Additionally, recombinase-activating gene 1(-/-) splenocytes can mediate Ab-dependent cellular cytotoxicity against this tumor in the presence of bound anti-TCR Abs. IFN-gamma knockout mice demonstrated a requirement for IFN-gamma, probably via generation of IgG2c Abs, in vaccine-induced tumor protection. IFN-gamma knockout mice were not protected by immunization and had a severe impairment in IgG2c Ab production in response to immunization. Although mock-depleted anti-TCR Abs could transfer tumor protection, IgG2c-deficient anti-TCR Abs were unable to transfer tumor protection to wild-type mice. These results suggest that TCR-KLH vaccine-induced tumor protection in the C6VL system is primarily attributable to the induction of IgG2c Abs and humoral immunity.