重组恒河猴抗α(4)β(7)单克隆抗体的初步体内疗效研究。
Preliminary in vivo efficacy studies of a recombinant rhesus anti-alpha(4)beta(7) monoclonal antibody.
作者信息
Pereira L E, Onlamoon N, Wang X, Wang R, Li J, Reimann K A, Villinger F, Pattanapanyasat K, Mori K, Ansari A A
机构信息
Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Room 2309 WMB, 101 Woodruff Circle, Atlanta, GA 30322, USA.
出版信息
Cell Immunol. 2009;259(2):165-76. doi: 10.1016/j.cellimm.2009.06.012. Epub 2009 Jun 26.
Abstract
Recent findings established that primary targets of HIV/SIV are lymphoid cells within the gastrointestinal (GI) tract. Focus has therefore shifted to T-cells expressing alpha(4)beta(7) integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of alpha(4)beta(7)+ T-cells in HIV/SIV pathogenesis include their depletion or blockade of their synthesis, binding and/or homing capabilities in vivo. Such studies can ideally be conducted in rhesus macaques (RM), the non-human primate model of AIDS. Characterization of alpha(4)beta(7) expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naïve and TEM (effector memory) T-cells. High densities were observed on TCM (central memory) T-cells. Intravenous administration of a single 50mg/kg dose of recombinant rhesus alpha(4)beta(7) antibody resulted in significant initial decline of alpha(4)beta(7)+ lymphocytes and sustained coating of the alpha(4)beta(7) receptor in both the periphery and GI tissues.
摘要
最近的研究结果表明，HIV/SIV的主要靶细胞是胃肠道（GI）内的淋巴细胞。因此，研究重点已转向表达α(4)β(7)整合素的T细胞，该整合素通过与黏膜血管地址素细胞黏附分子-1（MAdCAM-1）结合促进向胃肠道的迁移。更好地理解α(4)β(7)+ T细胞在HIV/SIV发病机制中作用的方法包括在体内耗尽这些细胞或阻断其合成、结合和/或归巢能力。此类研究理想情况下可在恒河猴（RM）中进行，RM是艾滋病的非人灵长类动物模型。对RM血液和胃肠道组织中细胞谱系上α(
相似文献
1
Preliminary in vivo efficacy studies of a recombinant rhesus anti-alpha(4)beta(7) monoclonal antibody.重组恒河猴抗α(4)β(7)单克隆抗体的初步体内疗效研究。
Cell Immunol. 2009;259(2):165-76. doi: 10.1016/j.cellimm.2009.06.012. Epub 2009 Jun 26.
2
Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus Macaques.在恒河猴感染猴免疫缺陷病毒的急性期阻断干扰素α后，慢性淋巴细胞活化减少。
J Virol. 2018 Apr 13;92(9). doi: 10.1128/JVI.01760-17. Print 2018 May 1.
3
Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.体内CD8 + T淋巴细胞耗竭对控制型与进展型猴免疫缺陷病毒感染猕猴的不同影响
J Virol. 2015 Sep;89(17):8677-86. doi: 10.1128/JVI.00869-15. Epub 2015 Jun 10.
4
Initiation of Antiretroviral Therapy Restores CD4+ T Memory Stem Cell Homeostasis in Simian Immunodeficiency Virus-Infected Macaques.抗逆转录病毒疗法的启动可恢复感染猿猴免疫缺陷病毒的猕猴体内CD4 + T记忆干细胞的稳态。
J Virol. 2016 Jul 11;90(15):6699-6708. doi: 10.1128/JVI.00492-16. Print 2016 Aug 1.
5
Blocking of α4β7 gut-homing integrin during acute infection leads to decreased plasma and gastrointestinal tissue viral loads in simian immunodeficiency virus-infected rhesus macaques.在急性感染期间阻断 α4β7 肠道归巢整合素可导致感染猴免疫缺陷病毒的恒河猴的血浆和胃肠道组织病毒载量降低。
J Immunol. 2011 Jan 15;186(2):1044-59. doi: 10.4049/jimmunol.1003052. Epub 2010 Dec 13.
6
Elite Control, Gut CD4 T Cell Sparing, and Enhanced Mucosal T Cell Responses in Macaca nemestrina Infected by a Simian Immunodeficiency Virus Lacking a gp41 Trafficking Motif.感染缺乏gp41转运基序的猿猴免疫缺陷病毒的豚尾猕猴中的精英控制、肠道CD4 T细胞保留及增强的黏膜T细胞反应
J Virol. 2015 Oct;89(20):10156-75. doi: 10.1128/JVI.01134-15. Epub 2015 Jul 29.
7
Cytokine/Chemokine responses in activated CD4+ and CD8+ T cells isolated from peripheral blood, bone marrow, and axillary lymph nodes during acute simian immunodeficiency virus infection.在急性猴免疫缺陷病毒感染期间，从外周血、骨髓和腋窝淋巴结中分离的激活的 CD4+和 CD8+T 细胞中的细胞因子/趋化因子反应。
J Virol. 2014 Aug;88(16):9442-57. doi: 10.1128/JVI.00774-14. Epub 2014 Jun 11.
8
Interleukin-21 administration to rhesus macaques chronically infected with simian immunodeficiency virus increases cytotoxic effector molecules in T cells and NK cells and enhances B cell function without increasing immune activation or viral replication.白细胞介素-21 给药恒河猴慢性感染猴免疫缺陷病毒增加细胞毒性效应分子在 T 细胞和 NK 细胞和增强 B 细胞功能而不增加免疫激活或病毒复制。
Vaccine. 2011 Nov 15;29(49):9229-38. doi: 10.1016/j.vaccine.2011.09.118. Epub 2011 Oct 11.
9
Diverse host responses and outcomes following simian immunodeficiency virus SIVmac239 infection in sooty mangabeys and rhesus macaques.在乌黑白眉猴和恒河猴中感染猿猴免疫缺陷病毒SIVmac239后出现的多种宿主反应和结果。
J Virol. 1998 Dec;72(12):9597-611. doi: 10.1128/JVI.72.12.9597-9611.1998.
引用本文的文献
1
Vedolizumab and ART in recent HIV-1 infection unveil the role of α4β7 in reservoir size.维得利珠单抗联合抗逆转录病毒疗法治疗新近感染 HIV-1 可揭示 α4β7 在储存库大小中的作用。
JCI Insight. 2024 Jul 9;9(16):e182312. doi: 10.1172/jci.insight.182312.
2
Early treatment with anti-αβ antibody facilitates increased gut macrophage maturity in SIV-infected rhesus macaques.早期使用抗-αβ 抗体可促进 SIV 感染恒河猴肠道巨噬细胞成熟度增加。
Front Immunol. 2022 Nov 1;13:1001727. doi: 10.3389/fimmu.2022.1001727. eCollection 2022.
3
Blocking αβ integrin delays viral rebound in SHIV-infected macaques treated with anti-HIV broadly neutralizing antibodies.阻断 αβ 整合素可延迟接受抗 HIV 广泛中和抗体治疗的感染 SHIV 的猕猴中的病毒反弹。
Sci Transl Med. 2021 Aug 18;13(607). doi: 10.1126/scitranslmed.abf7201.
4
Mechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy.抗 α4β7 抗体治疗后 SIV 治疗后控制的机制基础。
PLoS Comput Biol. 2021 Jun 9;17(6):e1009031. doi: 10.1371/journal.pcbi.1009031. eCollection 2021 Jun.
5
Frequency of Effector Memory Cells Expressing Integrin αβ Is Associated With TGF-β1 Levels in Therapy Naïve HIV Infected Women With Low CD4 T Cell Count.在未经治疗的、CD4 细胞计数较低的 HIV 感染女性中，表达整合素 αβ 的效应记忆细胞的频率与 TGF-β1 水平相关。
Front Immunol. 2021 Mar 22;12:651122. doi: 10.3389/fimmu.2021.651122. eCollection 2021.
6
Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV-infected rhesus macaques.黏膜整合素 α4β7 阻断未能减少 SIV 感染恒河猴中的病毒储存库的定植和大小。
FASEB J. 2021 Feb;35(2):e21282. doi: 10.1096/fj.202002235R.
7
Anti-αβ monoclonal antibody-conjugated nanoparticles block integrin αβ on intravaginal T cells in rhesus macaques.抗 αβ 单克隆抗体偶联纳米颗粒阻断恒河猴阴道内 T 细胞上的整合素 αβ。
Sci Adv. 2020 Aug 21;6(34). doi: 10.1126/sciadv.abb9853. Print 2020 Aug.
8
T Cells in the Female Reproductive Tract Can Both Block and Facilitate HIV Transmission.女性生殖道中的T细胞既能阻断也能促进HIV传播。
Curr Immunol Rev. 2019;15(1):36-40. doi: 10.2174/1573395514666180807113928.
9
Preliminary Studies on Immune Response and Viral Pathogenesis of Zika Virus in Rhesus Macaques.恒河猴中寨卡病毒免疫反应和病毒致病机制的初步研究
Pathogens. 2018 Aug 20;7(3):70. doi: 10.3390/pathogens7030070.
10
Core-shell nanoparticles for targeted and combination antiretroviral activity in gut-homing T cells.用于靶向和联合抗逆转录病毒活性的核壳纳米颗粒在肠道归巢 T 细胞中。
Nanomedicine. 2018 Oct;14(7):2143-2153. doi: 10.1016/j.nano.2018.06.005. Epub 2018 Jun 28.
本文引用的文献
1
Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo.肠系膜基质淋巴结细胞对于体内归巢至肠道的T细胞的产生至关重要。
J Exp Med. 2008 Oct 27;205(11):2483-90. doi: 10.1084/jem.20080039. Epub 2008 Oct 13.
2
T-cell recruitment to the intestinal mucosa.T细胞向肠道黏膜的募集。
Trends Immunol. 2008 Nov;29(11):514-22. doi: 10.1016/j.it.2008.08.003.
3
Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin.使用MLN0002（一种针对α4β7整合素的人源化抗体）治疗活动性克罗恩病。
Clin Gastroenterol Hepatol. 2008 Dec;6(12):1370-7. doi: 10.1016/j.cgh.2008.06.007. Epub 2008 Oct 1.
4
Sooty mangabeys and rhesus macaques exhibit significant divergent natural killer cell responses during both acute and chronic phases of SIV infection.在猴免疫缺陷病毒（SIV）感染的急性期和慢性期，乌黑白眉猴和恒河猴均表现出显著不同的自然杀伤细胞反应。
Cell Immunol. 2008;254(1):10-9. doi: 10.1016/j.cellimm.2008.06.006. Epub 2008 Jul 21.
5
How HIV guts the immune system.HIV如何破坏免疫系统。
N Engl J Med. 2008 May 22;358(21):2287-9. doi: 10.1056/NEJMcibr0802134.
6
Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys.活化的CD4 + T细胞的可用性决定了自然感染SIV的乌黑白眉猴的病毒血症水平。
J Clin Invest. 2008 Jun;118(6):2039-49. doi: 10.1172/JCI33814.
7
HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells.HIV-1包膜蛋白与整合素α4β7结合并通过其发出信号，整合素α4β7是外周T细胞的肠道黏膜归巢受体。
Nat Immunol. 2008 Mar;9(3):301-9. doi: 10.1038/ni1566. Epub 2008 Feb 10.
8
Vitamin A metabolites induce gut-homing FoxP3+ regulatory T cells.维生素A代谢产物可诱导归巢至肠道的FoxP3+调节性T细胞。
J Immunol. 2007 Sep 15;179(6):3724-33. doi: 10.4049/jimmunol.179.6.3724.
9
All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation.在存在高水平共刺激的情况下，全反式维甲酸介导调节性T细胞的生长、分化增强及向肠道归巢。
J Exp Med. 2007 Aug 6;204(8):1765-74. doi: 10.1084/jem.20070719. Epub 2007 Jul 9.
10
A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism.一群功能特化的黏膜CD103⁺树突状细胞通过转化生长因子-β和视黄酸依赖机制诱导Foxp3⁺调节性T细胞。
J Exp Med. 2007 Aug 6;204(8):1757-64. doi: 10.1084/jem.20070590. Epub 2007 Jul 9.
Zotero 插件