Mtb-Specific HLA-E-Restricted T Cells Are Induced during Mtb Infection but Not after BCG Administration in Non-Human Primates and Humans

被引：1

作者：

Voogd, Linda ^{[1
]}

van Wolfswinkel, Marjolein ^{[1
]}

Satti, Iman ^{[2
]}

White, Andrew D. ^{[3
]}

Dijkman, Karin ^{[4
]}

Gela, Anele ^{[5
,6
]}

van Meijgaarden, Krista E. ^{[1
]}

Franken, Kees L. M. C. ^{[1
]}

Marshall, Julia L. ^{[2
]}

Ottenhoff, Tom H. M. ^{[1
]}

Scriba, Thomas J. ^{[5
,6
]}

Mcshane, Helen ^{[2
]}

Sharpe, Sally A. ^{[3
]}

Verreck, Frank A. W. ^{[4
]}

Joosten, Simone A. ^{[1
]}

机构：

[1] Leiden Univ Med Ctr, Leiden Univ Ctr Infect Dis, NL-2333 ZA Leiden, Netherlands

[2] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England

[3] UK Hlth Secur Agcy, Salisbury SP4 0JG, England

[4] Biomed Primate Res Ctr, NL-2288 GJ Rijswijk, Netherlands

[5] Univ Cape Town, Inst Infect Dis & Mol Med, South African TB Vaccine Initiat, ZA-7925 Cape Town, South Africa

[6] Univ Cape Town, Dept Pathol, Div Immunol, ZA-7925 Cape Town, South Africa

来源：

VACCINES | 2024年 / 12卷 / 10期

基金：

美国国家卫生研究院;

关键词：

HLA-E; vaccine; BCG; tuberculosis; T cells; IDENTIFICATION; TUBERCULOSIS; PREVENTION; EXPRESSION; RESPONSES;

D O I：

10.3390/vaccines12101129

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Novel vaccines targeting the world's deadliest pathogen Mycobacterium tuberculosis (Mtb) are urgently needed as the efficacy of the Bacillus Calmette-Gu & eacute;rin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted Mtb-specific CD8+ T cells can control intracellular Mtb growth, making HLA-E a promising vaccine target for Mtb. Methods: In this study, we evaluated the frequency and phenotype of HLA-E-restricted Mtb-specific CD4+/CD8+ T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. Results: BCG vaccination followed by Mtb challenge in NHPs did not affect the frequency of circulating and local HLA-E-Mtb CD4+ and CD8+ T cells, and we saw the same in humans receiving BCG. HLA-E-Mtb T cell frequencies were significantly increased after Mtb challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Conclusions: Together, HLA-E-Mtb-restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after Mtb infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.

引用

页数：17

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