CD4 and CD8 T-lymphocyte recognition of prostate specific antigen in granulomatous prostatitis
CD4 and CD8 T-lymphocyte recognition of prostate specific antigen in granulomatous prostatitis
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DOI：
10.1097/00002371-200403000-00007
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发表时间：
2004-03-01
影响因子：
3.9
通讯作者：
Alexander, RB
中科院分区：
文献类型：
--
作者：
Klyushnenkova, EN;Ponniah, S;Alexander, RB
为了开发前列腺癌的免疫疗法，许多小组正在探索疫苗接种策略以诱导针对前列腺特异性抗原（PSA）的免疫应答。为了确定PSA的T细胞识别是否可能是自然发生的人类疾病的特征，我们研究了前列腺炎患者，前列腺炎是一种对男性临床综合征知之甚少的疾病，有证据表明可能发生针对前列腺的免疫反应。我们希望确定这些患者中是否可能发生对PSA的T细胞应答。我们使用纯化的PSA作为抗原，从一名肉芽肿性前列腺炎患者的外周血单个核细胞（PBMC）中产生长期T细胞系。选择了几种CD 4（+）和CD 8（+）TcR α/β（+）T细胞系的PSA反应性，如通过响应于由经辐照的自体PBMC呈递的PSA的IFN-γ分泌的至少三倍增加所测量的。CD 4和CD 8 T细胞系分别在HLA-DR β 1 *1501和HLA-beta*0702的背景下识别PSA。使用EBV-B细胞系证实了该细胞系的特异性和HLA限制性，该细胞系感染了重组PSA表达牛痘病毒，并且还通过逆转录病毒转染工程化以表达PSA。由对照载体感染的HLA匹配的靶标以及HLA错配的PSA表达靶标不诱导应答。数据表明，PSA特异性T细胞存在于该肉芽肿性前列腺炎患者的PBMC中，该患者可能自然地表现出针对前列腺的免疫应答类型，这是前列腺癌免疫治疗的目标。然而，I类限制性表位尚未被证明在前列腺癌细胞的表面上表达。据我们所知，这是首次证明HLA-DRB 1 *1501-或HLA-B*0702-限制性的PSA应答，并扩展了HLA分子的数量，以适应PSA抗原作为前列腺癌免疫治疗的候选疫苗的使用。
In order to develop immunotherapies for prostate cancer, many groups are exploring vaccination strategies to induce an immune response against prostate specific antigen (PSA). To determine if T-cell recognition of PSA might be a feature of a naturally occurring human disease, we have studied patients with prostatitis, a poorly understood clinical syndrome of men in which there is evidence that an immune response directed against the prostate may be occurring. We wished to determine if a T-cell response to PSA might be occurring in these patients. We generated long-term T-cell lines from peripheral blood mononuclear cells (PBMC) of one patient with granulomatous prostatitis using purified PSA as an antigen. Several CD4(+) and CD8(+) TcR alpha/beta(+) T-cell lines were selected for PSA reactivity as measured by at least a threefold increase in IFN-gamma secretion in response to PSA presented by irradiated autologous PBMC. CD4 and CD8 T-cell lines recognized PSA in the context of HLA-DRbeta1*1501 and HLA-beta*0702, respectively. The specificity and HLA restriction of the lines was confirmed using EBV-B cell lines infected with a recombinant PSA-expressing vaccinia virus and also engineered to express PSA by retroviral transfection. HLA-matched targets infected by control vector as well as HLA-mismatched PSA-expressing targets did not induce the response. The data demonstrate that PSA-specific T cells are present in the PBMC of this patient with granulomatous prostatitis, who may be manifesting naturally the type of immune response directed at the prostate that is the goal of prostate cancer immunotherapy. However, the Class I-restricted epitope has not yet been demonstrated to be expressed on the surface of prostate cancer cells. To our knowledge, this is the first demonstration of HLA-DRB1*1501- or HLA-B*0702-restricted responses to PSA and extends the number of HLA molecules accommodating the use of PSA antigen as a candidate vaccine for prostate cancer immunotherapy.