Comparison of blood and lymph node cells after intramuscular injection with HIV envelope immunogens.
Comparison of blood and lymph node cells after intramuscular injection with HIV envelope immunogens.
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DOI：
10.3389/fimmu.2022.991509
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发表时间：
2022
影响因子：
7.3
通讯作者：
Pollock, Katrina M.
中科院分区：
文献类型：
--
作者：
Day, Suzanne;Kaur, Charandeep;Cheeseman, Hannah M.;de Groot, Emily;McFarlane, Leon R.;Tanaka, Maniola;Coelho, Sofia;Cole, Tom;Lemm, Nana-Marie;Lim, Adrian;Sanders, Rogier W.;Asquith, Becca;Shattock, Robin J.;Pollock, Katrina M.
通过合理的抗原设计利用淋巴结中的CD 4 + T细胞帮助可以在实验性HIV免疫期间增强广泛中和抗体（bNAbs）的形成。由于直接研究的困难，该过程仍然是隐藏的，而临床研究则侧重于血液中的反应，作为次级淋巴组织的代表。为了解决这一问题，在实验性HIV免疫原研究（欧洲艾滋病疫苗倡议EAVI2020_01研究，NCT 04046978）中，使用超声引导细针抽吸法从11名HIV阴性参与者的腋窝淋巴结中收集淋巴结细胞（LNC）。在肌内注射基于HIV包膜糖蛋白的HIV Env Mosaic免疫原并与脂质体toll样受体-4佐剂（单磷酰脂质A）组合后，从淋巴结和血液（PBMC）中收集细胞。从同一供体的血液和淋巴结中同时取样的细胞进行表型、功能和抗原特异性比较。无监督聚类分析显示，与PBMC相比，LNC在丰度、分布和功能反应方面存在组织特异性差异。单核细胞几乎不存在于LNC中，与CD 8 + T细胞相比，其显著富集CD 4 + T细胞。具有生发中心特征的T滤泡辅助细胞在LNC中富集，LNC含有特异性CD 4+和CD 8 + T细胞亚群，包括在单次注射HIV Env Mosaic免疫原与佐剂组合后应答的CD 4 + T细胞。组织特异性的差异，响应MHC-II依赖的超抗原，葡萄球菌肠毒素B，表明血液和淋巴结之间的抗原呈递功能的分歧。LNC在表型和功能上与PBMC不同，表明全血仅是T细胞对免疫的淋巴应答的有限代表。淋巴结中的HIV特异性CD 4 + T细胞在实验性注射HIV免疫原后可快速诱导。通过重复实验性HIV免疫，监测LNC中CD 4 + T细胞记忆的演变，可以表明最有可能成功诱导HIV特异性bNAb的策略。
Harnessing CD4+ T cell help in the lymph nodes through rational antigen design could enhance formation of broadly neutralizing antibodies (bNAbs) during experimental HIV immunization. This process has remained hidden due to difficulty with direct study, with clinical studies instead focusing on responses in the blood as a proxy for the secondary lymphoid tissue. To address this, lymph node cells (LNC) were collected using ultrasound guided fine needle aspiration of axillary lymph nodes from 11 HIV negative participants in an experimental HIV immunogen study (European AIDS Vaccine Initiative EAVI2020_01 study, NCT04046978). Cells from lymph node and blood (PBMC), were collected after intramuscular injection with HIV Env Mosaic immunogens based on HIV Envelope glycoprotein and combined with a liposomal toll-like receptor-4 adjuvant; monophosphoryl lipid A. Simultaneously sampled cells from both blood and lymph node in the same donors were compared for phenotype, function, and antigen-specificity. Unsupervised cluster analysis revealed tissue-specific differences in abundance, distribution, and functional response of LNC compared with PBMC. Monocytes were virtually absent from LNC, which were significantly enriched for CD4+ T cells compared with CD8+ T cells. T follicular helper cells with germinal center features were enriched in LNC, which contained specific CD4+ and CD8+ T cell subsets including CD4+ T cells that responded after a single injection with HIV Env Mosaic immunogens combined with adjuvant. Tissue-specific differences in response to an MHC-II dependent superantigen, staphylococcal enterotoxin B, indicated divergence in antigen presentation function between blood and lymph node. LNC are phenotypically and functionally distinct from PBMC, suggesting that whole blood is only a limited proxy of the T cell lymphatic response to immunization. HIV-specific CD4+ T cells in the lymph node are rapidly inducible upon experimental injection with HIV immunogens. Monitoring evolution of CD4+ T cell memory in LNC with repeated experimental HIV immunization could indicate the strategies most likely to be successful in inducing HIV-specific bNAbs.
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影响因子：
16.8
作者：
Kong, Leopold;Lee, Jeong Hyun;Doores, Katie J.;Murin, Charles D.;Julien, Jean-Philippe;McBride, Ryan;Liu, Yan;Marozsan, Andre;Cupo, Albert;Klasse, Per-Johan;Hoffenberg, Simon;Caulfield, Michael;King, C. Richter;Hua, Yuanzi;Le, Khoa M.;Khayat, Reza;Deller, Marc C.;Clayton, Thomas;Tien, Henry;Feizi, Ten;Sanders, Rogier W.;Paulson, James C.;Moore, John P.;Stanfield, Robyn L.;Burton, Dennis R.;Ward, Andrew B.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
生发中心B细胞对SARS-COV-2的反应。
DOI：
10.1038/s41577-021-00657-1
发表时间：
2022-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Laidlaw BJ;Ellebedy AH
通讯作者：
Ellebedy AH
DOI：
10.1073/pnas.1205834109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Bollig, Nadine;Bruestle, Anne;Lohoff, Michael
通讯作者：
Lohoff, Michael
影响因子：
3.7
作者：
Reiss, Samantha;Baxter, Amy E.;Kaufmann, Daniel E.
通讯作者：
Kaufmann, Daniel E.
影响因子：
2.2
作者：
Havenar-Daughton, Colin;Newton, Isabel G.;Crotty, Shane
通讯作者：
Crotty, Shane