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首页> 外文期刊>Virology Journal >Natural OX40L expressed on human T cell leukemia virus type-I-immortalized T cell lines interferes with infection of activated peripheral blood mononuclear cells by CCR5-utilizing human immunodeficiency virus
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Natural OX40L expressed on human T cell leukemia virus type-I-immortalized T cell lines interferes with infection of activated peripheral blood mononuclear cells by CCR5-utilizing human immunodeficiency virus

机译：在人类T细胞白血病病毒I型永生T细胞系上表达的天然OX40L通过利用CCR5利用人类免疫缺陷病毒来干扰活化的外周血单个核细胞的感染

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Background OX40 ligand (OX40L) co-stimulates and differentiates T cells via ligation of OX40 that is transiently induced on T cells upon activation, resulting in prolonged T cell survival and enhanced cytokine production by T cells. This view has led to the targeting of OX40 as a strategy to boost antigen specific T cells in the context of vaccination. In addition, the ligation of OX40 has also been shown to inhibit infection by CCR5-utilizing (R5) but not CXCR4-utilizing (X4) human immunodeficiency virus type-1 (HIV-1) via enhancement of production of CCR5-binding β-chemokines. It was reasoned that human T cell leukemia virus type-I (HTLV-1) immortalized T cell lines that express high levels of OX40L could serve as an unique source of physiologically functional OX40L. The fact that HTLV-1+ T cell lines simultaneously also express high levels of OX40 suggested a potential limitation. Results Results of our studies showed that HTLV-1+ T cell lines bound exogenous OX40 but not OX40L, indicating that HTLV-1+ T cell lines express an active form of OX40L but an inactive form of OX40. Anti-OX40 non-blocking monoclonal antibody (mAb), but not blocking mAb, stained HTLV-1+ T cell lines, suggesting that the OX40 might be saturated with endogenous OX40L. Functionality of the OX40L was confirmed by the fact that a paraformaldehyde (PFA)-fixed HTLV-1+ T cell lines inhibited the infection of autologous activated peripheral blood mononuclear cells (PBMCs) with R5 HIV-1 which was reversed by either anti-OX40L blocking mAb or a mixture of neutralizing mAbs against CCR5-binding β-chemokines. Conclusions Altogether, these results demonstrated that autologous T cell lines immortalized by HTLV-1 can be utilized as a conventional source of physiologically functional OX40L.
机译：背景OX40配体（OX40L）通过激活后在T细胞上短暂诱导的OX40的连接来共同刺激T细胞并使其分化，从而延长T细胞存活时间并提高T细胞产生的细胞因子。该观点导致了以OX40为靶标作为在疫苗接种背景下增强抗原特异性T细胞的策略。此外，OX40的连接还显示通过增强CCR5结合β-的产生来抑制CCR5利用（R5）感染，但CXCR4利用（X4）1型人类免疫缺陷病毒（HIV-1）不能抑制感染。趋化因子。有理由认为，表达高水平OX40L的I型人T细胞白血病病毒（HTLV-1）永生T细胞系可以作为生理功能OX40L的独特来源。 HTLV-1 + T细胞系同时也表达高水平的OX40的事实表明存在潜在的局限性。结果我们的研究结果表明，HTLV-1 + T细胞系结合外源OX40，但不结合OX40L，这表明HTLV-1 + T细胞系表达了一种活性形式的OX40L但是非活性形式的OX40。 HTLV-1 + T细胞系具有抗OX40的非阻断性单克隆抗体（mAb），但未阻断性的mAb，提示OX40可能被内源性OX40L饱和。 OX40L的功能通过以下事实得到证实：低聚甲醛（PFA）固定的HTLV-1 + T细胞系抑制了R5 HIV-1对自体激活的外周血单个核细胞（PBMC）的感染。可通过抗OX40L阻断性mAb或中和性mAb对抗CCR5结合β趋化因子的混合物逆转。结论综上所述，这些结果表明，被HTLV-1无限增殖的自体T细胞系可以用作生理功能OX40L的常规来源。

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