Comparison of blood and lymph node cells after intramuscular injection with HIV envelope immunogens
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background:
Harnessing CD4+ T cell help in the lymph nodes through rational antigen design could enhance formation of broadly neutralising antibodies (bNAbs) during experimental HIV immunisation. This process has remained hidden due to difficulty with direct study, with clinical studies instead focusing on responses in the blood as a proxy for the secondary lymphoid tissue.
Methods:
To address this, lymph node cells (LNC) were collected using ultrasound guided fine needle aspiration of axillary lymph nodes from 11 HIV negative participants in an experimental HIV immunogen study (European AIDS Vaccine Initiative EAVI2020_01 study, NCT04046978). Cells from lymph node and blood (PBMC), were collected after intramuscular injection with HIV Env Mosaic immunogens based on HIV Envelope glycoprotein and combined with a liposomal toll-like receptor-4 adjuvant; monophosphoryl lipid A. Simultaneously sampled cells from both blood and lymph node in the same donors were compared for phenotype, function, and antigen-specificity.
Results:
Unsupervised cluster analysis revealed tissue-specific differences in abundance, distribution, and functional response of LNC compared with PBMC. Monocytes were virtually absent from LNC, which were significantly enriched for CD4+ T cells compared with CD8+ T cells. T follicular helper cells with germinal centre features were enriched in LNC, which contained specific CD4+ and CD8+ T cell subsets including CD4+ T cells that responded after a single injection with HIV Env Mosaic immunogens combined with adjuvant. Tissue-specific differences in response to an MHC-II dependent superantigen, staphylococcal enterotoxin B, indicated divergence in antigen presentation function between blood and lymph node.
Conclusions:
LNC are phenotypically and functionally distinct from PBMC, suggesting that whole blood is only a limited proxy of the T cell lymphatic response to immunisation. HIV-specific CD4+ T cells in the lymph node are rapidly inducible upon experimental injection with HIV immunogens. Monitoring evolution of CD4+ T cell memory in LNC with repeated experimental HIV immunisation could indicate the strategies most likely to be successful in inducing HIV-specific bNAbs.
Harnessing CD4+ T cell help in the lymph nodes through rational antigen design could enhance formation of broadly neutralising antibodies (bNAbs) during experimental HIV immunisation. This process has remained hidden due to difficulty with direct study, with clinical studies instead focusing on responses in the blood as a proxy for the secondary lymphoid tissue.
Methods:
To address this, lymph node cells (LNC) were collected using ultrasound guided fine needle aspiration of axillary lymph nodes from 11 HIV negative participants in an experimental HIV immunogen study (European AIDS Vaccine Initiative EAVI2020_01 study, NCT04046978). Cells from lymph node and blood (PBMC), were collected after intramuscular injection with HIV Env Mosaic immunogens based on HIV Envelope glycoprotein and combined with a liposomal toll-like receptor-4 adjuvant; monophosphoryl lipid A. Simultaneously sampled cells from both blood and lymph node in the same donors were compared for phenotype, function, and antigen-specificity.
Results:
Unsupervised cluster analysis revealed tissue-specific differences in abundance, distribution, and functional response of LNC compared with PBMC. Monocytes were virtually absent from LNC, which were significantly enriched for CD4+ T cells compared with CD8+ T cells. T follicular helper cells with germinal centre features were enriched in LNC, which contained specific CD4+ and CD8+ T cell subsets including CD4+ T cells that responded after a single injection with HIV Env Mosaic immunogens combined with adjuvant. Tissue-specific differences in response to an MHC-II dependent superantigen, staphylococcal enterotoxin B, indicated divergence in antigen presentation function between blood and lymph node.
Conclusions:
LNC are phenotypically and functionally distinct from PBMC, suggesting that whole blood is only a limited proxy of the T cell lymphatic response to immunisation. HIV-specific CD4+ T cells in the lymph node are rapidly inducible upon experimental injection with HIV immunogens. Monitoring evolution of CD4+ T cell memory in LNC with repeated experimental HIV immunisation could indicate the strategies most likely to be successful in inducing HIV-specific bNAbs.
Date Issued
2022-10-05
Date Acceptance
2022-08-17
Citation
Frontiers in Immunology, 2022, 13, pp.1-17
ISSN
1664-3224
Publisher
Frontiers Media
Start Page
1
End Page
17
Journal / Book Title
Frontiers in Immunology
Volume
13
Copyright Statement
© 2022 Day, Kaur, Cheeseman, de Groot, McFarlane, Tanaka, Coelho, Cole, Lemm, Lim, Sanders, Asquith, Shattock and Pollock. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Wellcome Trust
European Commission Directorate-General for Research and Innovation
Identifier
https://www.frontiersin.org/articles/10.3389/fimmu.2022.991509/full
Grant Number
RDA02
103865/Z/14/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
lymph node cells
vaccine
HIV
T follicular helper cell
T cell
HIV envelope
CD4+T cell
envelope
TRANSCRIPTION FACTOR IRF4
FOLLICULAR HELPER-CELLS
T-CELLS
CRYSTAL-STRUCTURE
RESPONSES
REVEALS
CD4+ T cell
HIV
HIV envelope
T cell
T follicular helper cell
envelope
lymph node cells
vaccine
Humans
AIDS Vaccines
Antibodies, Neutralizing
Broadly Neutralizing Antibodies
Glycoproteins
HIV Antigens
HIV Infections
Injections, Intramuscular
Leukocytes, Mononuclear
Lymph Nodes
Superantigens
Toll-Like Receptors
Lymph Nodes
Leukocytes, Mononuclear
Humans
HIV Infections
Glycoproteins
AIDS Vaccines
HIV Antigens
Superantigens
Injections, Intramuscular
Toll-Like Receptors
Antibodies, Neutralizing
Broadly Neutralizing Antibodies
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
991509
Date Publish Online
2022-10-05