SUPPRESSION OF ACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS LONG TERMINAL REPEAT BY CD8(+) T-CELLS IS NOT LENTIVIRUS SPECIFIC
SUPPRESSION OF ACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS LONG TERMINAL REPEAT BY CD8(+) T-CELLS IS NOT LENTIVIRUS SPECIFIC
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DOI：
10.1089/aid.1995.11.1321
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发表时间：
1995-11-01
影响因子：
1.5
通讯作者：
ROSENTHAL, KL
中科院分区：
文献类型：
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作者：
COPELAND, KFT;MCKAY, PJ;ROSENTHAL, KL
HIV-1感染者的CD8(+)T细胞能有效抑制HIV-1在CD4(+)T细胞中的复制。为了阐明这种抑制的分子事件，我们使用了指导氯霉素乙酰转移酶基因(CAT)的HIV-1 LTR在使用人Jurkat T细胞的瞬时转染试验中。除了患者CD8(+)T淋巴细胞的上清液(CD_4(+)和GT；350/亩L)外，还检测了一例患者的CD_8(+)T淋巴细胞经疱疹病毒塞米里(HV)介导转化后的T细胞克隆的上清液。两种来源的培养上清液对TAT或佛波醇酯和钙离子载体的促有丝分裂激活反应对LTR介导的基因表达的抑制程度相似。CD8(+)T淋巴细胞对慢病毒LTRs的抑制作用不是慢病毒所特有的，因为HTLV-I LTRs和RSV LTRs对有丝分裂原的转录均被有效抑制。在检测CD8(+)T细胞来源的上清液对核因子kappa B介导的激活的影响时，HIV-1核因子kappaB元件的食用者明显被患者CD8(+)淋巴细胞和人类免疫缺陷病毒(HVS)来源的CD8(+)克隆的上清液所抑制。因此，CD8(+)T淋巴细胞的抑制性质似乎不是慢病毒启动子所特有的，可能是通过核因子kappa B元件介导的抑制效应。
CD8(+) T lymphocytes of HIV-1-infected individuals can efficiently suppress HIV-1 replication in CD4(+) T lymphocytes. To elucidate the molecular events underlying this suppression, we have used the HIV-1 LTR directing the chloramphenicol acetyltransferase gene (CAT) in transient transfection assays using human Jurkat T cells. In addition to supernatants of patient CD8(+) T lymphocytes (CD4(+) > 350/mu l), supernatant of a T cell clone derived by Herpesvirus saimiri (HVS)-mediated transformation of CD8(+) T lymphocytes of a patient demonstrating inhibition of virus replication were examined. Similar levels of inhibition of LTR-mediated gene expression in response to Tat or mitogenic activation with phorbol ester and calcium ionophore were observed by supernatants of both sources. The inhibitory effect of CD8(+) T lymphocytes was not exclusive to lentiviral LTRs since transcription of both the HTLV-I LTR and RSV LTR in response to mitogen was effectively inhibited. In examination of the influence of CD8(+) T cell-derived supernatant on NF kappa B-mediated activation, a diner of the HIV-1 NF kappa B elements directing CAT was markedly inhibited by supernatants of both patient CD8(+) lymphocytes and the HVS-derived CD8(+) clone. Thus the inhibitory nature of CD8(+) T lymphocytes appears not to be specific to lentiviral promoters and may mediate an inhibitory effect via the NF kappa B element.