The neutralizing function of the anti-HTLV-1 antibody is essential in preventing in vivo transmission of HTLV-1 to human T cells in NOD-SCID/γcnull (NOG) mice.
The neutralizing function of the anti-HTLV-1 antibody is essential in preventing in vivo transmission of HTLV-1 to human T cells in NOD-SCID/γcnull (NOG) mice.
复制标题
抗 HTLV-1 抗体的中和功能对于防止 HTLV-1 在 NOD-SCID/γcnull (NOG) 小鼠体内传播至人 T 细胞至关重要。
DOI：
10.1186/s12977-014-0074-z
复制
发表时间：
2014-08-28
期刊：
影响因子：
3.3
通讯作者：
Tanaka Y
中科院分区：
文献类型：
--
作者：
Saito M;Tanaka R;Fujii H;Kodama A;Takahashi Y;Matsuzaki T;Takashima H;Tanaka Y
人类T细胞白血病病毒1型（HTLV-1）可引起肿瘤性和炎性疾病，包括成人T细胞白血病和HTLV-1相关的脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）。由于这些危及生命和致残的疾病尚未治愈，因此预防新的HTLV-1感染非常重要。在这项研究中，我们建立了一个简单的人源化小鼠模型HTLV-1感染的预防和治疗干预措施进行评估。在该模型中，将HTLV-1阴性正常人外周血单核细胞（PBMC）与丝裂霉素处理的HTLV-1产生T细胞一起直接移植到严重免疫缺陷NOD-SCID/γcnull（NOG）小鼠的脾脏中。使用该模型，我们测试了特异于HTLV-1的单克隆抗体（mAb）以及从HAM/TSP患者分离的人IgG（HAM-IgG）在预防HTLV-1感染中的功效。在人细胞移植前1小时和移植后24小时，腹膜内接种各抗体样品。在第14天，测试从小鼠脾分离的人PBMC的HTLV-1感染。然而，从未处理的小鼠或用同种型对照mAb处理的小鼠中分离的新鲜的CD 4阳性和CD 8阳性T细胞、包被gp 46、gagp 19的HTLV-1非中和mAb和正常人IgG均被HTLV-1感染;用HTLV-1中和抗gp 46 mAb或HAM-IgG处理的小鼠未被感染。我们的数据表明，抗体的中和功能，而不是抗原特异性，是防止HTLV-1的体内传播所必需的。本动物模型还可用于体内评估用作HTLV-1感染预防和治疗干预的候选分子的功效。本文的在线版本（doi：10.1186/s12977-014-0074-z）包含补充材料，可供授权用户使用。
Human T-cell leukemia virus type 1 (HTLV-1) causes both neoplastic and inflammatory diseases, including adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Because these life-threatening and disabling diseases are not yet curable, it is important to prevent new HTLV-1 infections. In this study, we have established a simple humanized mouse model of HTLV-1 infection for evaluating prophylactic and therapeutic interventions. In this model, HTLV-1-negative normal human peripheral blood mononuclear cells (PBMCs) are transplanted directly into the spleens of severely immunodeficient NOD-SCID/γcnull (NOG) mice, together with mitomycin-treated HTLV-1-producing T cells. Using this model, we tested the efficacy of monoclonal antibodies (mAbs) specific to HTLV-1 as well as human IgG isolated from HAM/TSP patients (HAM-IgG) in preventing HTLV-1-infection. One hour before and 24 h after transplantation of the human cells, each antibody sample was inoculated intraperitoneally. On day 14, human PBMCs isolated from the mouse spleens were tested for HTLV-1 infection. Whereas fresh CD4-positive and CD8-positive T cells isolated from untreated mice or mice treated with isotype control mAb, HTLV-1 non-neutralizing mAbs to envelope gp46, gag p19, and normal human IgG were all infected with HTLV-1; the mice treated with either HTLV-1 neutralizing anti-gp46 mAb or HAM-IgG did not become infected. Our data indicate that the neutralizing function of the antibody, but not the antigen specificity, is essential for preventing the in vivo transmission of HTLV-1. The present animal model will also be useful for the in vivo evaluation of the efficacy of candidate molecules to be used as prophylactic and therapeutic intervention against HTLV-1 infection. The online version of this article (doi:10.1186/s12977-014-0074-z) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
5.5
作者：
Akari, H;Suzuki, T;Yoshikawa, Y
通讯作者：
Yoshikawa, Y
影响因子：
5.4
作者：
Kinpara, Shuichi;Hasegawa, Atsuhiko;Kannagi, Mari
通讯作者：
Kannagi, Mari
影响因子：
6.4
作者：
IBRAHIM, F;FIETTE, L;BOMFORD, R
通讯作者：
BOMFORD, R
影响因子：
6.4
作者：
LAIRMORE, MD;ROBERTS, B;COCKERELL, GL
通讯作者：
COCKERELL, GL
影响因子：
4.6
作者：
Sondergaard, H.;Kvist, P. H.;Haase, C.
通讯作者：
Haase, C.