Cham Lamin B, Torrez Dulgeroff Laughing Bear, Tal Michal Caspi, Adomati Tom, Li Fanghui, Bhat Hilal, Huang Anfei, Lang Philipp A, Moreno Mary E, Rivera Jose M, Galkina Sofiya A, Kosikova Galina, Stoddart Cheryl A, McCune Joseph M, Myers Lara M, Weissman Irving L, Lang Karl S, Hasenkrug Kim J
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany.
Institute for Stem Cell Biology and Regenerative Medicine, and Ludwig Center for Cancer Stem Cell Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell Rep. 2020 Apr 14;31(2):107494. doi: 10.1016/j.celrep.2020.03.058.
Paradoxically, early host responses to infection include the upregulation of the antiphagocytic molecule, CD47. This suggests that CD47 blockade could enhance antigen presentation and subsequent immune responses. Indeed, mice treated with anti-CD47 monoclonal antibody following lymphocytic choriomeningitis virus infections show increased activation of both macrophages and dendritic cells (DCs), enhancement of the kinetics and potency of CD8 T cell responses, and significantly improved virus control. Treatment efficacy is critically dependent on both APCs and CD8 T cells. In preliminary results from one of two cohorts of humanized mice infected with HIV-1 for 6 weeks, CD47 blockade reduces plasma p24 levels and restores CD4 T cell counts. The results indicate that CD47 blockade not only enhances the function of innate immune cells but also links to adaptive immune responses through improved APC function. As such, immunotherapy by CD47 blockade may have broad applicability to treat a wide range of infectious diseases.
矛盾的是，宿主对感染的早期反应包括抗吞噬分子CD47的上调。这表明阻断CD47可以增强抗原呈递及随后的免疫反应。事实上，感染淋巴细胞性脉络丛脑膜炎病毒后用抗CD47单克隆抗体治疗的小鼠，巨噬细胞和树突状细胞（DC）的激活增加，CD8 T细胞反应的动力学和效力增强，病毒控制显著改善。治疗效果严重依赖于抗原呈递细胞（APC）和CD8 T细胞。在感染HIV-1 6周的两批人源化小鼠中，其中一批的初步结果显示，阻断CD47可降低血浆p24水平并恢复CD4 T细胞计数。结果表明，阻断CD47不仅增强了先天免疫细胞的功能，还通过改善APC功能与适应性免疫反应相关联。因此，通过阻断CD47进行免疫治疗可能具有广泛的适用性，可用于治疗多种传染病。
