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青少年卡介苗复种可诱导对结核分枝杆菌的 CD4 T 细胞反应表型转变。

Adolescent BCG revaccination induces a phenotypic shift in CD4 T cell responses to Mycobacterium tuberculosis.

机构信息

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa.

出版信息

Nat Commun. 2024 Jun 18;15(1):5191. doi: 10.1038/s41467-024-49050-1.

DOI:10.1038/s41467-024-49050-1
PMID:38890283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11189459/
Abstract

A recent clinical trial demonstrated that Bacille Calmette-Guérin (BCG) revaccination of adolescents reduced the risk of sustained infection with Mycobacterium tuberculosis (M.tb). In a companion phase 1b trial, HVTN 602/Aeras A-042, we characterize in-depth the cellular responses to BCG revaccination or to a H4:IC31 vaccine boost to identify T cell subsets that could be responsible for the protection observed. High-dimensional clustering analysis of cells profiled using a 26-color flow cytometric panel show marked increases in five effector memory CD4 T cell subpopulations (T) after BCG revaccination, two of which are highly polyfunctional. CITE-Seq single-cell analysis shows that the activated subsets include an abundant cluster of Th1 cells with migratory potential. Additionally, a small cluster of Th17 T cells induced by BCG revaccination expresses high levels of CD103; these may represent recirculating tissue-resident memory cells that could provide pulmonary immune protection. Together, these results identify unique populations of CD4 T cells with potential to be immune correlates of protection conferred by BCG revaccination.

摘要

最近的一项临床试验表明，卡介苗（BCG）复种可降低青少年持续感染结核分枝杆菌（M.tb）的风险。在一项伴随的 1b 期试验 HVTN 602/Aeras A-042 中，我们深入研究了细胞对 BCG 复种或 H4:IC31 疫苗加强的反应，以确定可能导致观察到的保护作用的 T 细胞亚群。使用 26 色流式细胞术面板对细胞进行分析的高维聚类分析显示，BCG 复种后五种效应记忆 CD4 T 细胞亚群（T 细胞）显著增加，其中两种具有高度多功能性。CITE-Seq 单细胞分析表明，激活的亚群包括具有迁移潜力的大量 Th1 细胞簇。此外，BCG 复种诱导的一小簇 Th17 T 细胞表达高水平的 CD103；这些可能代表循环组织驻留记忆细胞，可提供肺部免疫保护。总之，这些结果确定了具有潜在成为 BCG 复种所赋予保护作用的免疫相关性的独特 CD4 T 细胞群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/f31518c0950d/41467_2024_49050_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/ac7102bccb56/41467_2024_49050_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/3f5c6973d27a/41467_2024_49050_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/f80a41526641/41467_2024_49050_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/fef68b1195b9/41467_2024_49050_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/f31518c0950d/41467_2024_49050_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/ac7102bccb56/41467_2024_49050_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/3f5c6973d27a/41467_2024_49050_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/f80a41526641/41467_2024_49050_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/fef68b1195b9/41467_2024_49050_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c4/11189459/f31518c0950d/41467_2024_49050_Fig5_HTML.jpg

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