Human postmortem studies reveal tissue-specific differences amongst TB-patient groups
Human postmortem studies reveal tissue-specific differences amongst TB-patient groups
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DOI：
10.1101/2023.03.14.532701
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发表时间：
2023-03
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通讯作者：
Gift Ahimbisibwe;Marjorie Nakibuule;Marvin Martin Ssejoba;David Oyamo;Rose Mulwana;Josephine Nabulime;Febronius Babirye;Abdusalaamu Kizito;H. Lekuya;Akello Suzan Adakun;R. Lukande;A. Kyazze;I. A. Biraro;S. Cose
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作者：
Gift Ahimbisibwe;Marjorie Nakibuule;Marvin Martin Ssejoba;David Oyamo;Rose Mulwana;Josephine Nabulime;Febronius Babirye;Abdusalaamu Kizito;H. Lekuya;Akello Suzan Adakun;R. Lukande;A. Kyazze;I. A. Biraro;S. Cose
如果我们要在结核病研究中开辟新的领域，我们需要完全了解人类感染部位发生的情况。死后研究给我们提供了一个机会，可以比较同一个体内病变组织和非病变组织中的受累组织和未受累组织。我们研究了在乌干达的Mulago和Kiruddu国家转诊医院进行尸检研究的可行性，以确定我们是否可以使用死后收集的免疫细胞进行免疫学研究。我们报告说，我们可以在8小时内同意近亲，进行死后程序和处理组织。免疫细胞在死亡后14小时内仍保持活力和功能。我们发现TB组内T细胞亚群的细微差异。肺和BAL中的CD 4 CD 69 + CD 103+耗竭与HIV相关，而BAL中的CD 8 CD 69 + CD 103-耗竭与TB相关。我们的数据显示了TB感染和TB未感染的人肺内和之间的组织驻留记忆T细胞的总体变化。总结在乌干达，验尸官领导的尸检研究是可能的，死亡后8小时内处理的样本来自尸检样本的细胞是活的和功能性的HIV相关的肺中CD 4 CD 69 +/CD 103 + T细胞亚群的消耗和BAL中与TB相关的BAL CD 8 CD 69 +/CD 103-消耗
If we are to break new grounds in TB research, we need to have a complete understanding of what is occurring at the site of infection in humans. Postmortem studies give us an opportunity compare involved and uninvolved tissues, in diseased and non-diseased tissues within the same individual. We examined the feasibility of carrying out a postmortem study in Mulago and Kiruddu National Referral Hospitals in Uganda, to determine whether we could use immune cells collected postmortem for immunological studies. We report that we can consent the Next-of-Kin, perform postmortem procedures and process tissues within 8hours. Immune cells remain viable and functional up to 14hours after death. We found subtle differences in T cell subsets within TB groups. Depletion of CD4 CD69+CD103+ depletion in lungs and BAL which is associated with HIV whereas CD8 CD69+CD103- depletion in BAL was associated with TB. Our data show overall changes Tissue Resident Memory T cells within, and between, TB-infected and TB-uninfected human lungs. Summary Coroner led postmortem studies are possible in Uganda, samples processed within 8hours from death Cells from samples collected postmortem are viable and functional HIV associated depletion of CD4 CD69+/CD103+ T cell subset in lungs and BAL CD8 CD69+/CD103- depletion in BAL associated with TB