BCG 疫苗接种对两项前瞻性队列研究中供体无限制 T 细胞的影响。

Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies.

机构信息

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

出版信息

EBioMedicine. 2022 Feb;76:103839. doi: 10.1016/j.ebiom.2022.103839. Epub 2022 Feb 8.

DOI:10.1016/j.ebiom.2022.103839

PMID:35149285

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8842032/

Abstract

BACKGROUND

Non-protein antigen classes can be presented to T cells by near-monomorphic antigen-presenting molecules such as CD1, MR1, and butyrophilin 3A1. Such T cells, referred to as donor unrestricted T (DURT) cells, typically express stereotypic T cell receptors. The near-unrestricted nature of DURT cell antigen recognition is of particular interest for vaccine development, and we sought to define the roles of DURT cells, including MR1-restricted MAIT cells, CD1b-restricted glucose monomycolate (GMM)-specific T cells, CD1d-restricted NKT cells, and γδ T cells, in vaccination against Mycobacterium tuberculosis.

METHODS

We compared and characterized DURT cells following primary bacille Calmette-Guerin (BCG) vaccination in a cohort of vaccinated and unvaccinated infants, as well as before and after BCG-revaccination in adults.

FINDINGS

BCG (re)vaccination did not modulate peripheral blood frequencies, T cell activation or memory profiles of MAIT cells, CD1b-restricted GMM-specific and germline-encoded mycolyl-reactive (GEM) cells or CD1d-restricted NKT cells. By contrast, primary BCG vaccination was associated with increased frequencies of γδ T cells as well as a novel subset of CD26CD161TRAV1-2 IFN-γ-expressing CD4 T cells in infants.

INTERPRETATION

Our findings, that most DURT cell populations were not modulated by BCG, do not preclude a role of BCG in modulating other qualitative aspects of DURT cells. More studies are required to understand the full potential of DURT cells in new TB vaccine strategies.

FUNDING

Aeras, the National Institutes of Health, and the Bill and Melinda Gates Foundation.

摘要

背景

非蛋白抗原类可以通过类似单态的抗原呈递分子，如 CD1、MR1 和丁酰基蛋白 3A1，呈递给 T 细胞。这种 T 细胞被称为供体无限制 T（DURT）细胞，通常表达定型 T 细胞受体。DURT 细胞抗原识别的近无限制性质对于疫苗开发特别感兴趣，我们试图确定 DURT 细胞的作用，包括 MR1 限制的 MAIT 细胞、CD1b 限制的葡萄糖单酰基（GMM）特异性 T 细胞、CD1d 限制的 NKT 细胞和 γδ T 细胞，在针对结核分枝杆菌的疫苗接种中的作用。

方法

我们比较并描述了接种卡介苗（BCG）前后的 DURT 细胞，包括接种和未接种婴儿以及成人 BCG 再接种前后的 DURT 细胞。

发现

BCG（再）接种不会调节 MAIT 细胞、CD1b 限制的 GMM 特异性和种系编码的分枝菌酰基反应性（GEM）细胞或 CD1d 限制的 NKT 细胞的外周血频率、T 细胞激活或记忆特征。相比之下，初次 BCG 接种与婴儿中 γδ T 细胞以及新型 CD26CD161TRAV1-2IFN-γ 表达 CD4 T 细胞亚群的频率增加有关。