瑞士巴塞尔大学Daniel D. Pinschewer团队发现，单次AAV递送的消除抗体引起的淋巴细胞亚群持久性消除，揭示了慢性病毒感染的免疫控制。该项研究成果于2024年12月23日在线发表在《免疫》杂志上。

研究人员表示，为了研究特定免疫细胞在感染、癌症和自身免疫中的作用，免疫学家通常使用单克隆消除抗体（消除-mAb）或基因工程小鼠模型（GEMM）。

为了生成一种结合了这两种方法的特定优点，并避免其某些缺陷的工具，研究人员设计了表达消除抗体的腺相关病毒载体（消除-AAV）。

单次消除-AAV给药可以持久性地消除小鼠中的淋巴细胞亚群，并避免了GEMM的附加缺陷，如B细胞缺乏动物中的边缘区缺陷。消除-AAV可以在不同遗传背景的动物中使用，且可以轻松地组合多种消除-AAV。

利用消除-AAV技术，研究人员展示了B细胞在慢性淋巴细胞性脉络膜脑膜炎病毒（LCMV）感染中，对CD4⁺和CD8⁺ T细胞反应的正常发挥至关重要。在B细胞被消除后，CD8⁺ T细胞未能抑制病毒血症，只有在抗体降低病毒载量时，它们才帮助解决慢性感染。该研究将消除-AAV定位为一种多功能的免疫学研究工具。

附：英文原文

Title: Durable lymphocyte subset elimination upon a single dose of AAV-delivered depletion antibody dissects immune control of chronic viral infection

Author: Anna Lena Kastner, Anna-Friederike Marx, Mirela Dimitrova, Tiago Abreu-Mota, Yusuf I. Ertuna, Weldy V. Bonilla, Karsten Stauffer, Marco Künzli, Ingrid Wagner, Mario Kreutzfeldt, Doron Merkler, Daniel D. Pinschewer

Issue&Volume: 2024-12-23

Abstract: To interrogate the role of specific immune cells in infection, cancer, and autoimmunity, immunologists commonly use monoclonal depletion antibodies (depletion-mAbs) or genetically engineered mouse models (GEMMs). To generate a tool that combines specific advantages and avoids select drawbacks of the two methods, we engineered adeno-associated viral vectors expressing depletion mAbs (depletion-AAVs). Single-dose depletion-AAV administration durably eliminated lymphocyte subsets in mice and avoided accessory deficiencies of GEMMs, such as marginal zone defects in B cell-deficient animals. Depletion-AAVs can be used in animals of different genetic backgrounds, and multiple depletion-AAVs can readily be combined. Exploiting depletion-AAV technology, we showed that B cells were required for unimpaired CD4+ and CD8+ T cell responses to chronic lymphocytic choriomeningitis virus (LCMV) infection. Upon B cell depletion, CD8+ T cells failed to suppress viremia, and they only helped resolve chronic infection when antibodies dampened viral loads. Our study positions depletion-AAVs as a versatile tool for immunological research.

DOI: 10.1016/j.immuni.2024.11.021

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00536-3