人特异性T细胞系间接识别猪抗原

SLA (swineleukocyteantigen )特异性CD4+T细胞系和自身APC以及猪PBMC共同孵育时 ,T细胞增殖反应很强 ,而同仅有自身APC或猪PBMC刺激时的T细胞增殖有显著差异。提示抗原特异性CD4+T细胞系以间接途径识别SLA抗原。该识别能被抗人CD4和HLAII类抗体阻断 ,而抗SLAII类抗体阻断作用很弱 ,表明HLAII类分子在间接识别中起重要作用 ,这一结果不同于直接从外周血中分离的未经抗原致敏的T细胞。直接识别猪APC递呈的抗原。有可能异种移植初期以直接识别为主导 ,随着移植物存活时间的延长逐渐转为间接识别     

T细胞识别的肿瘤抗原

在人类肿瘤中已鉴定出很多能为肿瘤特异性ＣＴＬ所能识别的抗原，在它们之中，有的由在肿瘤中表达但处于隐性状态下的基因所编码；有的则由肿瘤中的突变编码。多数人类肿瘤细胞上带有这种能为Ｔ细胞识别的抗原，应用这些抗原进行免疫接种将有一定的临床意义。     

建立猪MHCⅠ类抗原特异性人T细胞系的探讨

目的　建立间接识别中国版纳猪SLAⅠ类P1分子的特异性人T细胞系的方法 ,以进一步研究SLAⅠ类分子的间接识别在猪→人异种细胞性排斥中的作用。方法　以E·coli中表达并纯化的SLAⅠ类分子P1为抗原 ,体外反复刺激健康人PBMC ,3H TdR掺入法筛选特异性增殖的T细胞 ,FACS作表型初步分析。结果　初步测定健康人外周血版纳猪SLAⅠ类P1分子特异性T细胞反应频率约 6 .67× 1 0 - 7,所建 4个T细胞系表型均为TCRαβ+ ,其中 3株以CD4+ 为主 ,1株以CD8+ 为主。结论　利用E .coli表达的纯蛋白抗原可建立间接识别版纳猪SLAⅠ类P1分子的特异性人T细胞系。     

诱导人T细胞对猪抗原免疫耐受的体外实验研究

目的：探讨诱导人Ｔ细胞对猪抗原免疫耐受的状况。方法：通过建立人幼稚淋巴细胞与猪抗原递呈细胞混合培养模型,以淋巴细胞增殖实验及毒性实验,ＤＮＡ分析,淋巴细胞表面标志检测等手段,观测了幼稚淋巴细胞分化,发育过程中对异种负调细胞疫苗初次接触与再次刺激的免疫应答状况的变化。     

T细胞识别同种异型移植抗原的研究进展

移植是末期组织、器官功能衰竭最彻底的治疗措施。同种异体移植(allogeneic transplantation)是临床最常见的移植类型。在本质上,人类的同种异体移植排斥反应是由受者的T细胞介导的、针对移植抗原的免疫应答。这一免疫应答是通过受者T细胞表面的T细胞受体(T cell receptor,TCR)识别移植物     

人胎儿胸腺T细胞亚群抗原的表达及其定位—免疫组织化学研究

用免疫组织化学法和多种识别Ｔ细胞亚群的抗体，观察了１５例胎儿胸腺内Ｔ细胞亚群的抗原表达及其分布。结果表明，胸腺皮、髓质Ｔ细胞对Ｌｅｕ４抗体均呈阳性，但髓质部较强。Ｌｅｕ３ａ和Ｌｅｕ２ａ阳性细胞分布于胸腺皮持、髓质，但髓质部阳性数目少于皮质。ＡＩＧ３和ＮＫ阳性细胞均分布于髓质，皮质几乎为阴性，ＩＬ－２Ｒ细胞分布于被膜下、皮质和髓质。ＢｒｄＵ标记的细胞主要存在于皮质，特别是外皮质区。此外胸腺内还有γδ     

树突状细胞的发育、亚群及其对T细胞应答类型的调控

树突状细胞 (DC )的发育可分为未成熟和成熟两个阶段 ,未成熟DC在捕捉抗原后向外周淋巴组织的T细胞区迁移并成熟 ,成熟DC能表达丰富的MHC分子和协同刺激分子。未成熟DC通过诱导无能的和调节性T细胞导致免疫耐受 ,而成熟DC具有超强的激活初始T细胞能力。DC至少可分为三个亚群 ,不同亚群的DC在激活Th1/Th2、CTL应答方面存在差异 ,但最近的研究显示DC对T细胞应答类型的调控受多种因素的综合影响 :包括微生物的产物或佐剂、DC表面的信号受体、DC亚群、局部的微环境和附近T细胞及其他细胞产生的细胞因子。因此 ,目前认为DC的功能具有可塑性     

急性心肌梗塞患者外周血活性T淋巴细胞亚群的研究

目的：研究１５例急性心肌梗塞患者外周血淋细胞亚群和活性标志的变化。方法：流式细胞仪技术,结果：急性心肌梗塞患者外周血淋巴细胞ＣＤ３＾＋ＤＲ＾＋和ＣＤ４＾＋和ＤＲ＾＋百分率明显高于对照组。结论：急性心肌梗塞患者存在免疫功能紊乱,辅助性Ｔ淋巴细胞处于高活性状态。     

移植排斥反应中的直接识别与间接识别

近年来, 器官移植事业在不断的发展, 但怎样解决移植器官的排斥问题, 一直是阻挡着器官移植继续进展的一大难题。众所周知, 由于人体免疫系统的作用, 被移植的器官绝大部分终究将被排斥掉。这个排斥的过程, 首先是树突状细胞(DC)在抗同种异体移植物的免疫应答过程中提呈抗原, 激活受体的T细胞; 然后是受体的免疫系统(主要是T细胞 )对同种异体移植物的识别和活化; 结果是T细胞介导的针对同种异体移植物的免疫应答通过多种机制直接杀伤细胞或是分泌细胞因子活化免疫系统从而导致炎症, 最终使移植物被排斥掉。而对同种异体移植物的主要组…     

Human Helper T Cell Lines Established by Coculture of Normal Human Cord Leukocytes with an HTLV-Il-infected Rabbit Leukocyte Cell Line (Ra-IIA)

Three helper T cell lines, designated CR -IIA (CR-IIA-1, CR-IIA- 2, and CR-IIA-3), were established by coculturing nor mal human cord leukocytes with a lethally irradiated HTLV II (human T lymphotropic virus type II)- infected rabbit leukocyte cell line (Ra-IIA). CR IIA had a normal human karyotype and expressed the surface markers CD3(+), CD4(+), CD8(-), CD19(-), CD25(+) and HLA- DR(+), confirming their helper T cell nature. CR- IIA cells were all free of Epstein- Barr virus nuclear antigen and were im-muno reactive with serum samples from HTLV- I- or HTLV-Il- infected patients and with anti HTLV- I, p19 or p24 anti body. The provirus genome of HTLV-II was detected in these cell lines by the polymerase chain reaction combined with a digoxigenin- enzyme- linked immunosorbent assay. Electron microscopy of CR-IIA-1 cells revealed a few im mature type C virus particles. These results suggest that HTLV- II was transmitted from the infected rabbit leukocyte cell line to human cord helper T lymphocytes with the development of immortalized HTLV - II- producing T cell lines. Acta Pathol Jpn 42: 347–352, 1992.     

Difference in the ability of HLA serum to react with T and B lymphocyte populations

The ability of HLA sera to react with T and B lymphocytes of human blood was studied. The lymphocytes were separated by removal of one of the cell populations. The method of rosette formation was used, followed by centrifugation in a density gradient and adsorption of B lymphocytes on synthetic fiber. After removal of the B cells the cytotoxic activity of the HLA sera was reduced. Removal of T lymphocytes did not affect the result of the lymphocytotoxic test. It is postulated that B lymphocytes contain more determinants of HLA antigens than T lymphocytes.Laboratory of Immunohematology, Central Institute of Hematology and Blood Transfusion, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Kosyakov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 6, pp. 698–699, June, 1976.     

Complexity of Human Immune Response Profiles for CD4+ T Cell Epitopes from the Diabetes Autoantigen GAD65

Complex protein antigens contain multiple potential T cell recognition epitopes, which are generated through a processing pathway involving partial antigen degradation via proteases, binding to MHC molecules, and display on the APC surface, followed by recognition via the T cell receptor. We have investigated recognition of the GAD65 protein, one of the well-characterized autoantigens in type I diabetes, among individuals carrying the HLA-DR4 haplo-types characteristic of susceptibility to IDDM. Using sets of 20-mer peptides spanning the GAD65 molecule, multiple immunostimulatory epitopes were identified, with diverse class II DR molecules functioning as the restriction element. The majority of T cell responses were restricted by DRB1 molecules; however, DRB4 restricted responses were also observed. Antigen-specific T cell clones and lines were derived from peripheral blood samples of pre-diabetic and IDDM patients and T cell recognition and response were measured. Highly variable proliferative and cytokine release profiles were observed, even among T cells specific for a single GAD65 epitope.     

Genetic Immunization Maps T Cell (Auto)Immune Responses to Self Antigens Homologous to Exogenous Proteins

Genetic immunization represents a new tool for investigating physiological and pathological immune responses. Here we used genetic immunization with naked DNA to study the immune relevance of aminoacid sequence homologies by evaluating the outcome of immunization to a viral protein homologous to an HLA molecule. The viral protein was Balf2, a protein of Epstein-Barr virus (EBV) that shares aminoacid sequence homology with the HLA allele DRB1*0801. After genetic immunization of BALB/c mice with a construct encoding Balf2, we analyzed T cell responses of immunized mice. We found that cross-reactive proliferative and cytotoxic responses were raised to the homologous sequence as expressed by HLA-DRB1*0801. Furthermore, preferential secretion of Th1-type pro-inflammatory cytokines occurred. This strategy can allow rapid screening of interactive immune networks involving aminoacid sequence homologies between organisms.     

HIV-1-Specific CD4+ T Cell Responses in Chronically HIV-1 Infected Blippers on Antiretroviral Therapy in Relation to Viral Replication Following Treatment Interruption

The impact of transient viral load blips on anti-HIV-1 immune responses and on HIV-1 rebound following treatment interruption (TI) is not known. Clinical and immunological parameters were measured during 40 weeks of antiretroviral therapy (ART) and following TI in an observational cohort of 16 chronically HIV-1-infected subjects with or without observed viral load blips during ART. During therapy, blips in seven subjects were associated with higher anti-HIV-1 (p24) CD4⁺ T cell lymphoproliferative responses (p = 0.04), without a significant difference in T cell activation or total anti-HIV-1 CD8⁺ T cell interferon-γ (IFN-γ) responses when compared to nine matched non-blippers. Therapy interruption resulted in a significantly higher viral rebound in blippers by 8 week despite retention of higher lymphoproliferative p24 responses (p = 0.01) and a rise in CD3⁺ T cell activation (p = 0.04) and anti-HIV-1 CD8⁺ T cell responses in blippers by week 4 when compared to non-blippers. Past week 4 of interruption, therapy re-initiation criteria were also met by a higher frequency in blippers by week 14 (p < 0.04) with no difference between groups by week 24. These data support that blippers have higher anti-HIV lymphoproliferative responses while on ART but experience equal to higher viral rebound as compared to matched non-blippers upon TI.     

T cell Responses to Enterovirus Antigens and to β-cell Autoantigens in Unaffected Children Positive for IDDM-Associated Autoantibodies

Enterovirus infections have been implicated in the pathogenesis of IDDM in a number of studies. The aim of the present study was to evaluate whether the cellular immune response to enterovirus antigens is abnormal in children who test positive for IDDM-associated autoantibodies. Lymphocyte proliferation responses were analysed to enterovirus antigens and to a panel of β-cell autoantigen preparations in 31 non-diabetic ICA and/or GAD65 antibody-positive children and in 19 ICA/GAD65-negative control children. The responses to highly purified enteroviruses did not differ between autoantibody (AA)-positive and -negative subjects. However, proliferation responses to coxsackievirus-infected cell lysate, which also included non-structural proteins of the virus, were higher in AA-positive than in AA-negative subjects (P<0.05). This difference was most marked in children carrying the HLA-DQB1*02 allele (P=0.01). AA-positive subjects also had higher responses to one of the three GAD65 antigen preparations compared to AA-negative subjects (P<0.05). Proliferation responses to the adenovirus hexon protein did not differ between the groups. These results show that the increased responses to virus infected cell lysates are associated with early phases of β-cell autoimmunity.     

Human CD8+ cytotoxic T cell responses to adenovirus capsid proteins

Adenoviruses (Ads) cause fatal disease in allogeneic stem cell transplant recipients, but there is no established therapy. Ad-specific CD8+ T cells were detected in PBMC from healthy adults at a mean frequency of 77 per 10(5) CD8+ T cells (range 8-260) by interferon-gamma ELISPOT and cytokine flow cytometry assays. CD8+ T cell lines from 7 of 7 donors exhibited MHC-class-I-restricted killing of targets expressing the capsid protein hexon. In contrast, cytotoxicity against the capsid proteins fiber and penton base was weaker or not detected. Two HLA-A2-restricted hexon epitopes and one HLA-B-restricted epitope were identified, all of which are adjacent to or overlap an HLA-DP4-restricted epitope in the highly conserved C-terminus. Thus, hexon is the immunodominant T cell target among capsid proteins and contains multiple C-terminal epitopes conserved among serotypes. These data support evaluation of donor lymphocyte infusions for treatment of Ad disease post-transplant.