中国HIV早期感染者CD+4CD+25Foxp3+调节性T淋巴细胞变化研究

目的 研究1年以内感染HIV的感染者(早期感染者,EHI)体内CD+4 CD+25 Foxp3+调节性T淋巴细胞水平及其与疾病进展相关性.方法 随机选取51例HIV感染者,依据感染时间及CD+4 T淋巴细胞水平分为3组:EHI组30例、HIV组15例、AIDS组6例,20名健康人作为对照组,各组对象的年龄、性别具有可比性.用EDTA抗凝管采集全血,应用FACSAria流式细胞仪及Foxp3染色试剂盒,检测外周血单个核细胞CD+4CD+25Foxp3+调节性T淋巴细胞表达水平,分析EHI者及全部HIV感染者CD+4 CD+25Foxp3+调节性T淋巴细胞表达水平与CD+4T淋巴细胞数量、病毒调定点、病毒载量及淋巴细胞活化水平间的相关性.结果 健康对照组、EHI组、HIV组及AIDS组CD+4C+25Foxp3+T淋巴细胞百分率逐级上升,其中EHI组CD+4CD+25Foxp3+T淋巴细胞百分率[3.79(2.11～5.43)%]低于AIDS组[8.09(4.90～8.90)%],差异有统计学意义(Z=-2.29,P=0.022);EHI组CD+4 CD+25Foxp3+T淋巴细胞百分率与病毒调定点正相关(r=0.479,P=0.038),与CD4T淋巴细胞计数呈负相关(r=-0.455,P=0.011),与CD+3 HLA+T淋巴细胞呈正相关(r=0.533,P=0.002).结论 中国EHI者CD+4 CD+25Foxp3+调节性T淋巴细胞百分率高与高病毒调定点及低CD+4 T淋巴细胞数量相关,提示CD+4 CD+25Fox3+调节性T淋巴细胞是加速HIV感染早期疾病进展的因素之一.     

Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs.

To investigate the effect of persistent HIV infection on the immune system, we studied leukocyte functions in 14 asymptomatic homosexual men (CDC group II/III) who were at least two years seropositive, but who still had normal numbers of circulating CD4+ T cells. Compared with age-matched heterosexual men and HIV-negative homosexual men, the CD4+ and CD8+ T cells from seropositive men showed decreased proliferation to anti-CD3 monoclonal antibody and decreased CD4+ T-helper activity on PWM-driven differentiation of normal donor B cells. Monocytes of HIV-infected homosexual men showed decreased accessory function on normal T cell proliferation induced by CD3 monoclonal antibody. The most striking defect in leukocyte functional activities was observed in the B cells of HIV-infected men. B cells of 13 out of 14 seropositive men failed to produce Ig in response to PWM in the presence of adequate allogeneic T-helper activity. These findings suggest that HIV induces severe immunological abnormalities in T cells, B cells, and antigen-presenting cells early in infection before CD4+ T cell numbers start to decline. Impaired immunological function in subclinically HIV-infected patients may have clinical implications for vaccination strategies, in particular the use of live vaccines in groups with a high prevalence of HIV seropositivity.     

Identification of a naturally processed HLA-DR-restricted T-helper epitope in Epstein-Barr virus nuclear antigen type 1

Epstein-Barr virus nuclear antigen type 1 (EBNA1), the only viral protein that is unequivocally expressed in all Epstein-Barr virus (EBV)-associated malignant diseases, is essential for viral DNA replication and maintenance of the viral episome in infected cells. A glycine-alanine repeat domain inhibits antigen processing through the ubiquitin-proteasome pathway for presentation on human leukocyte antigen (HLA) class I molecules. EBNA1 is not protected from the HLA class II processing pathway, and CD4+ HLA class II-restricted T cells recognize the antigen. CD4+ T-helper (Th) cells play critical roles in initiating, regulating, and maintaining immune responses against viral infections and tumors, so that inclusion of EBNA1 as a target antigen may improve immunotherapy for EBV-associated cancers. In this study, the authors used the TEPITOPE software program to predict promiscuous class II epitope candidates. After several HLA-DR-restricted peptides were identified by in vitro analysis of the T-cell response to synthetic peptides, a T-cell clone was established that was specific for one of the peptides. Functional studies were performed with this clone. The CD4+ T helper cells specific for the HLA-DR15-restricted peptide EBNA1(482) (AEGLRALLARSHVER) recognized naturally processed EBNA1 protein. This epitope was presented by several HLA-DR alleles, including DR4, DR7, and DR11. The inclusion of the promiscuous, naturally processed EBNA1(482) epitope in vaccine constructs could enhance immune responses against EBV-positive cancers.     

Identification of T-cell epitopes by a novel mRNA PCR-based epitope chase technique

The identification of specific viral and tumor antigen T-cell epitopes remains a challenge. Indeed, epitope mapping methods are generally costly and time-consuming. Thus, few techniques allow for efficient CD4+ T-lymphocyte epitope identification. Here, we introduce a novel polymerase chain reaction-based mRNA epitope identification method, called mPEC, to rapidly and precisely identify relevant T-cell epitopes recognized by CD8+ or CD4+ T lymphocytes. This method is based on the use of mRNA fragments synthesized from polymerase chain reaction-amplified cDNA with a choice of 3'end deletions. mRNA fragments are electroporated into autologous antigen-presenting cells to deduce an epitope's localization in a given protein antigen. Considering mRNA's sensitivity to degradation, we also inserted a defined epitope at the mRNA's 3'end to control for electroporated mRNA's integrity and its capacity to be translated. Using this method, we rapidly and successfully identified the specific epitope of 2 CD8+ and 1 CD4+ T-lymphocyte clones derived from influenza model antigens. Hence, mPEC could be used to identify new, in vivo-relevant T-cell epitopes for cancer immunotherapy and vaccination in general.     

新疆100例HIV／AIDS患者机体细胞免疫与合并机会性感染关系的研究

目的探讨人类免疫缺陷病毒（HIV）感染者和艾滋病（AIDS）患者机体细胞免疫与合并机会性感染的关系。方法总结新疆100例HIV／AIDS患者临床资料,分析CD3^＋、CD4^、CD8^＋细胞水平,及CD4^＋细胞数与发生机会性感染的关系。结果HIV／AIDS患者合并机会感染CD3^＋、CD4^＋细胞数明显低于未合并机会感染组且差异均具有统计学意义（t=-2．073,t=-4．087,P〈0．05）,CD8^＋、CD4^＋／CD8^＋比值则差异无统计学意义（P〉0．05）。CD3^＋细胞数与CD4^＋细胞数的变化呈正相关（r=0．481,P〈0．05）,与CD8^＋细胞数的变化呈高度正相关（r=0．954,P〈0．05）。CD4^＋细胞含量〈200个／μl时,发生机会性感染高于CD4^＋细胞含量为200—500个／μl时,且差异有统计学意义（r=17．272,P〈0．05）。在CD4^＋细胞含量〈200个μl的HIV／AIDS患者中以PCP的合并感染为最高27．27％,其次弓形虫和结核（22．73％,13．64％）。结论HIV／AIDS患者并发机会性感染与免疫抑制程度有关,CD4^＋的水平是目前监测机会性感染的重要参考依据,不同地区机会性感染疾病谱略有不同,临床可采取相应的预防性治疗措施。     

HIV/AIDS患者B7-H1的表达特点及与疾病进展关系研究

目的 研究HIV/AIDS患者外周血mDC及不同亚群T淋巴细胞B7-H1及PD-1的表达水平,分析其与疾病进展的相关性,探讨B7-H1及PD-1信号通路在HIV感染中的作用.方法 采集中国医科大学附属第一医院艾滋病研究所红丝带门诊36例未经抗病毒治疗的HIV/AIDS患者(无症状HIV组、AIDS组)及20名健康对照组...     

DNA vaccines encoding Ii-PADRE generates potent PADRE-specific CD4+ T-cell immune responses and enhances vaccine potency.

It is now clear that CD4+ T cells play a crucial role in the generation of CD8+ T effector and memory T-cell immune responses. In this study, we enhanced the CD4+ T-cell immune responses in mice by constructing a DNA vaccine encoding an invariant (Ii) chain in which the class II-associated Ii peptide (CLIP) region is replaced with a CD4+ T-helper epitope, PADRE (Ii-PADRE) (invariant Pan HLA-DR reactive epitope). C57BL/6 mice vaccinated with DNA encoding Ii-PADRE showed significantly greater PADRE-specific CD4+ T-cell immune responses than mice vaccinated with DNA encoding the Ii chain alone (Ii DNA). More important, administration of DNA encoding human papillomavirus (HPV) E6 or E7 antigen with DNA encoding Ii-PADRE led to significantly stronger E6- or E7-specific CD8+ T-cell immune responses and more potent protective and therapeutic anti-tumor effects against an E6/E7-expressing tumor model in mice than administration of E6 or E7 DNA with Ii DNA. Overall, our data indicate that administration of DNA vaccines with Ii-PADRE DNA represents an effective approach to enhancing the generation of CD4+ T cells and eliciting stronger antigen-specific CD8+ T-cell immune responses. Therefore, this strategy may be expected to have significant potential for clinical translation.     

T cell recognition of the A2 domain of coagulation factor VIII in hemophilia patients and healthy subjects.

Hemophilia A patients treated with coagulation factor VIII (FVIII), and also some healthy subjects, may develop anti-FVIII antibodies (Ab), whose synthesis is driven by FVIII-specific CD4+ T cells. Some Ab block the procoagulant function of FVIII (inhibitors). Many inhibitors recognize epitopes on the FVIII A2 domain. Here, we have sought to identify A2 epitopes recognized by CD4+ T cells. We tested the proliferative response of CD4+ blood lymphocytes (BL) from hemophilia patients and healthy subjects, to overlapping synthetic peptides spanning the A2 domain sequence. Many A2 peptides induced proliferative responses of CD4+ BL from one or more subjects. The peptide-induced responses were strongest in hemophilia patients with inhibitors, weakest in healthy subjects. A2 peptides comprising residues 371-400, 621-650 and 671-690 elicited frequent and strong responses in hemophilia A patients, and especially in those with inhibitors. Healthy subjects recognized frequently only the sequence 371-400. A three-dimensional model of the A2 domain suggests that these CD4+ epitope sequences have structural features typical of 'universal' CD4+ T epitopes.     

HIV/AIDS患者伴尖锐湿疣的治疗

目的观察CO2激光联合咪喹莫特乳膏治疗不同CD4+T淋巴细胞水平的HIV/AIDS患者伴尖锐湿疣的疗效。方法采用病例对照研究,普通尖锐湿疣患者为对照组、HIV/AIDS患者且CD4+T淋巴细胞计数在200 cells/μL以上为试验A组、HIV/AIDS患者且CD4+T淋巴细胞计数在200 cells/μL以下者为试验B组。3组患者均给予CO2激光联合咪喹莫特乳膏治疗。结果 CO2激光联合咪喹莫特乳膏治疗HIV/AIDS患者伴尖锐湿疣对试验A组疗效较试验B组好。试验A组患者治疗时间不低于12周,试验B组患者治疗时间大于12周;3组患者治愈率和复发率差异有统计学意义。结论对于CD4+T淋巴细胞小于200 cells/μL的HIV/AIDS患者尽快进行高效抗反转录病毒治疗(HAART),可待CD4+T淋巴细胞上升至大于200 cells/μL时,再进行治疗,可以降低尖锐湿疣的复发率,减少治疗次数。该类患者进行HAART是必要的。     

应用流式细胞仪研究HIV/AIDS患者的免疫状况

目的　探讨人类免疫缺陷病毒 ( human immunodeficiency virus,HIV)感染者和艾滋病 ( acquired immunodefi-ciency syndrome,AIDS)患者的免疫状况。方法　应用流式细胞仪 ( flow cytometer,FCM)四色荧光计数 ( CD4 5 +、CD3+、CD4 + 、CD8+ )检测 2 0例正常人、38例 HIV无症状感染者、2 4例 HIV有症状感染者和 2 1例 AIDS患者的外周血 CD4 + 、CD8+ 淋巴细胞 ,结合临床进行分析。　结果　 HIV无症状感染者、HIV有症状感染者和 AIDS患者的外周血 CD4 + 细胞数( 45 6± 99.8、2 87± 85 .3、4 5± 4 1 .9)及 CD4 + / CD8+比值 ( 0 .4 6± 0 .1 4、0 .39± 0 .1 5、0 .1 1± 0 .0 9)均明显低于正常人群的CD4 + 细胞数 ( 84 2± 2 64.1 ) ( P<0 .0 1 )及 CD4 + / CD8+ 比值 ( 1 .79± 0 .5 1 ) ( P<0 .0 1 ) ;二者随病程进展不断下降 ,且不同病程间差异明显。结论　CD4 +细胞绝对数和 CD4 + / CD8+比值可作为检测 HIV感染临床分期的重要指标     

Generating renal cancer-reactive T cells using dendritic cells (DCs) to present autologous tumor

Dendritic cells (DCs) have been used as professional antigen-presenting cells in vitro to prime T-cell responses. In this study, we generated both CD8+ and CD4+ renal cell carcinoma (RCC)-reactive T cells using a completely autologous system of DCs presenting engulfed whole-tumor cells. We compared DCs presenting RCC tumor cells in different preparations and found ultraviolet-irradiated apoptotic tumor cells to be more immunogenic than necrotic tumor cells or live untreated tumor cells in generating tumor-reactive T cells. In analyzing the T cells generated in this fashion, a CD8+ RCC-reactive T-cell clone generated from a patient recognized an epitope derived from fibroblast growth factor 5 in the context of human leukocyte antigen (HLA) B44*02. CD4+ T cells generated from another patient recognized multiple allogeneic RCC lines expressing HLA-DRbeta1*04, indicating a common shared tumor antigen presented by HLA-DRbeta1*04. The technique of using DCs to present whole-tumor cells can consistently generate both CD4+ and CD8+ RCC-reactive T cells for use in both antigen identification and therapeutic protocols.     

Number of T reg cells that differentiate does not increase upon encounter of agonist ligand on thymic epithelial cells

It has been reported that the differentiation of CD4+CD25+ regulatory T cells (T reg cells) can be induced by agonist peptide/major histocompatibility complex ligands in the thymus. Exploiting a transgenic mouse line wherein expression of a particular T cell epitope can be controlled temporally and quantitatively, we found that diversion of differentiating thymocytes into the FoxP3 T reg cell pathway by this agonist ligand was essentially nonexistent. However, CD4+CD25+ thymocytes were much less sensitive than their CD4+CD25- companions, by two to three orders of magnitude, to agonist-induced clonal deletion, such that their proportion increased, giving the false impression of induced differentiation. To account for these and prior observations, one can propose that differentiation along the CD4+CD25+ pathway is induced by cues other than recognition of self-agonist cues, which are poorly read by thymocytes, whose T cell receptors are conducive to selection toward the conventional CD4+CD25- lineage. Thus, selective survival, rather than induced differentiation, may explain the apparent enrichment observed here and in previous studies.     

载脂蛋白B mRNA编辑酶催化多肽样蛋白3GmRNA表达水平与HIV/AIDS患者疾病进展的相关性研究

目的 探讨河南省46例HIV/AIDS患者外周血单个核细胞载脂蛋白B mRNA编辑酶催化多肽样蛋白3G(APOBEC3G)mRNA表达水平与艾滋病疾病进展的相关性.方法 采用实时定量PCR方法检测HIV感染不同疾病进展期患者外周血单个核细胞APOBEC3G mRNA表达水平;采用流式细胞仪进行CD4+T淋巴细胞的绝对和相对计数;采用全自动载量仪检测血浆HIV病毒载量.结果 河南省46例HIV/AIDS患者外周血单个核细胞APOBEC3G mRNA水平明显低于健康对照(t=4.887,P<0.01),缓慢进展组APOBEC3G mRNA水平显著高于HIV组和AIDS组(P<0.05).HIV/AIDS患者APOBEC3G mRNA表达水平与CD4+T淋巴细胞数呈正相关(R2=0.190,P=0.002),与病毒载量呈负相关(R2=0.094,P=0.038).结论河南省HIV/AIDS患者外周血单个核细胞APOBEC3G mRNA表达水平与HIV感染疾病进程密切相关,APOBEC3G高表达可能是延缓疾病进程的保护性因素之一.     

Identification of a mutated fibronectin as a tumor antigen recognized by CD4+ T cells: its role in extracellular matrix formation and tumor metastasis

CD4+ T cells play an important role in orchestrating host immune responses against cancer, particularly by providing critical help for priming and extending the survival of CD8+ T cells. However, relatively little is known about major histocompatibility complex class II-restricted human tumor antigens capable of activating CD4+ T cells. Here, we describe the identification of a mutated fibronectin (FN) as a tumor antigen recognized by human histocompatibility leukocyte antigen-DR2-restricted CD4+ T cells. Deoxyribonucleic acid (DNA) sequencing analysis indicated that this gene contains a mutation that results in the substitution of lysine for glutamic acid and gives rise to a new T cell epitope recognized by CD4+ T cells. Tumor cells harboring the mutant FN resulted in the loss of FN matrix formation and the gain of metastatic potential based on the migration pattern compared with that of tumor cells that express wild-type FN. Additional experiments using cell lines stably expressing the mutated FN cDNA demonstrated that the point mutation in FN was responsible for the loss of FN staining in extracellular matrices and the enhancement of tumor cell migration. These findings represent the first demonstration that a mutated gene product recognized by CD4+ T cells is directly involved in tumor metastasis, which indicates the importance of CD4+ T cells in controlling the spread of tumor cells to distant anatomic sites.     

CD81和趋化因子CC受体5与丙型肝炎合并人类免疫缺陷病毒感染的相关性研究

目的 检测外周血CD4＋及CD8＋T淋巴细胞表面CD81、CCR5的表达,探讨与丙型肝炎病毒（HCV）单纯感染、人类免疫缺陷病毒（HIV）单纯感染和HCV/HIV合并感染的关系.方法 采用流式细胞术,检测HCV感染组（n=21）、HIV感染组（n=14）、HCV/HIV感染组（n=28）及正常对照组（n=30）人外周血CD4＋及CD8＋T淋巴细胞表面CD81和CCR5的表达.结果 与正常对照组相比,外周血CD4＋T淋巴细胞表面CD81,在HCV感染组表达变化不明显,而在HIV感染组和HCV/HIV合并感染组中低表达;CD8＋T淋巴细胞表面CD81,在HCV感染组、HIV感染组和HCV/HIV合并感染组中都呈高表达.外周血CD4＋T和CD8＋T淋巴细胞表面CCR5,在HIV感染组高表达,而在HCV感染组和HCV/HIV合并感染组中低表达.结论 HCV/HIV合并感染中,影响外周血CD4＋及CD8＋T淋巴细胞表面CCR5表达的主要因素是HCV感染;而合并感染对CD4＋及CD8＋T淋巴细胞表面CD81的表达,其影响作用是不相同的.     

HIV／AIDS患者CD4＋T淋巴细胞数的变化与外周血淋巴细胞总数的变量的关系研究

目的研究人免疫缺陷病毒（HIV）感染者和艾滋病（AIDS）患者CIM＋T淋巴细胞数的变化（△CD4＋T）和外周血淋巴细胞总数的变量（△TLC）的相关性,探讨用△TLC预测CD4＋T在监测HIV疾病进展和高效抗逆转录病毒治疗（HAART）疗效中发挥的作用。方法分析91例HIV／AIDS患者CD4＋T和TLC及△CD4＋T和△TLC的相关性,通过ROC面积、敏感度、特异度、阳性预测值和阴性预测值分析,寻找能有效预测CD4＋T淋巴细胞数〈200个／μl,〈350个／μl,时TLC的范围;△CD4＋T淋巴细胞数为50个／μl、100个／μl、200个／μl、300个／μl时△TLC的范围。结果91例HIV／AIDS患者CD4＋T和TLC相关系数r为0．716,P〈0．01;△TLC和△CD4＋T具有更强的相关性,相关系数r为0．809,P〈0．01。用1300个／μl和1700个／μl TLC预测CD4＋T200个／μl和350个／μl具有显著的预测价值。用△TLC 170个／μl、330个／μl、630个／μl、910个／μl分别预测△CD4＋T50个／μl、100个／μl、200个／μl、300个／μl,各项预测指标基本上在90％以上,显著高于相同时间下TLC预测CD4＋T的效果。结论人免疫缺陷病毒（HIV）感染者和艾滋病（AIDS）患者CD4＋T淋巴细胞数的变化（△CD4＋T）和外周血淋巴细胞总数的变量（△TLC）具有直线相关性。在条件匮乏的艾滋病高发区,可以应用△TLC预测△CD4＋T．比TLC更加直观、准确的反映HIV感染者疾病进展和评价AIDS患者HAART的疗效。     

中国HCV/HIV合并感染者T淋巴细胞表面CD81、CXCR3表达的研究

目的探讨T淋巴细胞表面受体CD81、CXCR3，在丙肝病毒（HCV）单纯感染，艾滋病病毒（HIV）单纯感染和HCV／HIV合并感染过程中的表达及意义。方法采用流式细胞术，检测HCV感染组（n=21），HIV感染组（n=14），HCV／HIV感染组（n=28）及正常对照组（n=30）人外周血CD4^＋T淋巴细胞和CD8^＋T淋巴细胞表面CD81、CXCR3的表达。结果HIV感染组及HCV／HIV合并感染组CD4^＋T细胞表面CD81、CXCR3表达显著降低（P〈0．001），CD8^＋T细胞表面CD81、CXCR3表达显著升高（P〈0．001）；HCV感染组CD4^＋及CD8^＋T细胞表面CXCR3表达轻度升高但差异不显著，CD81在CD4^＋T细胞表面轻度升高而在CD8^＋T细胞表面明显升高（P〈0．01）。结论中国HCV／HIV合并感染患者外周血T淋巴细胞表面受体CD81、CXCR3，在CD4^＋T细胞表面表达降低，而在CD8^＋T细胞表面表达升高。     

Virological and immunological effects of antioxidant treatment in patients with HIV infection

BACKGROUND: Intracellular oxidative stress in CD4+ lymphocytes due to disturbed glutathione homeostasis may lead to impaired lymphocyte functions and enhanced HIV replication in patients with HIV infection, especially in those with advanced immunodeficiency. The aim of the present study was to assess whether short-term, high-dose antioxidant treatment might have effects on immunological and virological parameters in patients with HIV infection. MATERIALS AND METHODS: In this pilot study, we examined virological and immunological effects of antioxidant combination treatment for 6 days with high doses of N-acetylcysteine (NAC) and vitamin C in 8 patients with HIV infection. The following were assayed before, during and after antioxidant treatment: HIV RNA plasma levels; numbers of CD4+, CD8+, and CD14+ leukocytes in blood; plasma thiols; intracellular glutathione redox status in CD4+ lymphocytes and CD14+ monocytes; lymphocyte proliferation; lymphocyte apoptosis and plasma levels of tumour necrosis factor (TNF)alpha; soluble TNF receptors and neopterin in plasma. RESULTS: No significant changes in HIV RNA plasma levels or CD4+ lymphocyte counts in blood were noted during antioxidant treatment in the patient group. However, in the 5 patients with the most advanced immunodeficiency (CD4+ lymphocyte counts < 200 x 106 L(-1)), a significant rise in CD4+ lymphocyte count, a reduction in HIV RNA plasma level of 0.8 log, an enhanced lymphocyte proliferation and an increased level of intracellular glutathione in CD4+ lymphocytes were found. No change in lymphocyte apoptosis was noted. CONCLUSIONS: Short-term, high-dose combination treatment with NAC and vitamin C in patients with HIV infection and advanced immunodeficiency lead to immunological and virological effects that might be of therapeutic value.     

B lymphocyte reconstitution after human bone marrow transplantation. Leu-1 antigen defines a distinct population of B lymphocytes.

Differences in the expression of Leu-1 (CD5) define two populations of recovering B cells after human marrow transplantation, Leu-1+ and Leu-1- B cells. The Leu-1+ B cells were polyclonal, of donor origin, and did not express detectable interleukin 2 receptor. Leu-1+ B cells generally appeared 2-4 wk after marrow grafting and often preceded the recovery of Leu-1- B cells. Acute and chronic graft vs. host disease (GvHD) resulted in the recovery of significantly fewer Leu-1+ B cells, whereas Leu-1- B cells were only decreased in acute GvHD. Multivariate analysis showed no significant effect of age, disease, prednisone or azathioprine, or ex vivo treatment of the marrow with anti-Leu-1 and complement on recovery of Leu-1+ and Leu-1- B cells, independent of the effects of GvHD. Leu-1+ B cells are a major lymphocyte population posttransplant. They may reflect a stage of differentiation of normal B cells or a separate B cell lineage.     

Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover

The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)-B27 patients. To understand further the nature of CD8+ T cell-mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27-restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10-specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.