Effective elicitation of human effector CD8+ T Cells in HLA-B*51:01 transgenic humanized mice after infection with HIV-1.
Effective elicitation of human effector CD8+ T Cells in HLA-B*51:01 transgenic humanized mice after infection with HIV-1.
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DOI：
10.1371/journal.pone.0042776
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Takiguchi M
中科院分区：
文献类型：
--
作者：
Sato Y;Nagata S;Takiguchi M
人源化小鼠有望作为感染性疾病发病机制体内研究的小动物模型。然而，众所周知，在仅移植有人CD 34+造血干细胞（HSC）的免疫缺陷小鼠中，人CD 8 + T细胞不能分化为效应细胞，因为人T细胞在小鼠胸腺中不受HLA训练。在此，我们通过将人CD 34 + HSC移植到HLA-B * 51：01转基因NOD/SCID/Jak 3 −/−小鼠（hNOK/B51 Tg小鼠）中建立了HLA-B * 51：01转基因人源化小鼠，并研究了是否会在小鼠或感染HIV-1 NL 4 -3的小鼠中诱导人效应CD 8 + T细胞。人CD 8 + T细胞中晚期效应记忆和效应子亚群（分别为CD 27低CD 28-CD 45 RA +/-CCR 7-和CD 27-CD 28-CD 45 RA +/-CCR 7-）的频率以及hNOK/B51 Tg和hNOK小鼠中表达CX 3CR 1和/或CXCR 1的人CD 8 + T细胞的频率无差异。与此相反，晚期效应记忆和效应CD 8 + T细胞亚群的频率和那些表达CX 3CR 1和/或CXCR 1的HIV-1感染的hNOK/B51 Tg小鼠显着高于未感染的，而这些亚群之间的HIV-1感染和未感染的hNOK小鼠没有差异。这些结果表明，hNOK/B51 Tg小鼠具有能够在病毒抗原刺激后分化为效应T细胞的CD 8 + T细胞，并且具有比hNOK小鼠更大的诱导效应CD 8 + T细胞的能力。
Humanized mice are expected to be useful as small animal models for in vivo studies on the pathogenesis of infectious diseases. However, it is well known that human CD8+ T cells cannot differentiate into effector cells in immunodeficient mice transplanted with only human CD34+ hematopoietic stem cells (HSCs), because human T cells are not educated by HLA in the mouse thymus. We here established HLA-B*51:01 transgenic humanized mice by transplanting human CD34+ HSCs into HLA-B*51:01 transgenic NOD/SCID/Jak3−/− mice (hNOK/B51Tg mice) and investigated whether human effector CD8+ T cells would be elicited in the mice or in those infected with HIV-1 NL4-3. There were no differences in the frequency of late effector memory and effector subsets (CD27lowCD28−CD45RA+/−CCR7− and CD27−CD28−CD45RA+/−CCR7−, respectively) among human CD8+ T cells and in that of human CD8+ T cells expressing CX3CR1 and/or CXCR1 between hNOK/B51Tg and hNOK mice. In contrast, the frequency of late effector memory and effector CD8+ T cell subsets and of those expressing CX3CR1 and/or CXCR1 was significantly higher in HIV-1-infected hNOK/B51Tg mice than in uninfected ones, whereas there was no difference in that of these subsets between HIV-1-infected and uninfected hNOK mice. These results suggest that hNOK/B51Tg mice had CD8+ T cells that were capable of differentiating into effector T cells after viral antigen stimulation and had a greater ability to elicit effector CD8+ T cells than hNOK ones.
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鼠T细胞对HLA识别的人CD8转基因调节。
影响因子：
15.3
作者：
Laface, Drake M.;Vestberg, Mikael;Yang, Young;Srivastava, Rakesh;Disanto, Jim;Flomenberg, Neal;Brown, Shafeeka;Sherman, Linda A.;Peterson, Per A.
通讯作者：
Peterson, Per A.
影响因子：
20.3
作者：
Gasser, O;Missiou, A;Hess, C
通讯作者：
Hess, C
影响因子：
20.3
作者：
Amir, Avital L.;D'Orsogna, Lloyd J. A.;Heemskerk, Mirjam H. M.
通讯作者：
Heemskerk, Mirjam H. M.
影响因子：
3.8
作者：
Eisenman, J;Ahdieh, M;Park, LS
通讯作者：
Park, LS
影响因子：
5.4
作者：
Brainard, Diana M.;Seung, Edward;Tager, Andrew M.
通讯作者：
Tager, Andrew M.