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Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer

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Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer. / Schulte, Sophia; Heide, Janna; Ackermann, Christin; Peine, Sven; Ramharter, Michael; Mackroth, Maria Sophia; Woost, Robin; Jacobs, Thomas; Schulze Zur Wiesch, Julian.

In: CLIN EXP IMMUNOL, Vol. 207, No. 2, 04.04.2022, p. 227-236.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schulte, S, Heide, J, Ackermann, C, Peine, S, Ramharter, M, Mackroth, MS, Woost, R, Jacobs, T & Schulze Zur Wiesch, J 2022, 'Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer', CLIN EXP IMMUNOL, vol. 207, no. 2, pp. 227-236. https://doi.org/10.1093/cei/uxab027

APA

Schulte, S., Heide, J., Ackermann, C., Peine, S., Ramharter, M., Mackroth, M. S., Woost, R., Jacobs, T., & Schulze Zur Wiesch, J. (2022). Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer. CLIN EXP IMMUNOL, 207(2), 227-236. https://doi.org/10.1093/cei/uxab027

Vancouver

Schulte S, Heide J, Ackermann C, Peine S, Ramharter M, Mackroth MS et al. Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer. CLIN EXP IMMUNOL. 2022 Apr 4;207(2):227-236. https://doi.org/10.1093/cei/uxab027

Bibtex

@article{ab496d7a75534ea6961250e33e49fc70,
title = "Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer",
abstract = "Relatively little is known about the ex vivo frequency and phenotype of the Plasmodium falciparum-specific CD4+ T-cell response in humans. The exported protein 1 (EXP1) is expressed by plasmodia at both, the liver stage and blood stage, of infection making it a potential target for CD4+ and CD8+ effector T cells. Here, a fluorochrome-labelled HLA-DRB1∗11:01-restriced MHC class II tetramer derived from the P. falciparum EXP1 (aa62-74) was established for ex vivo tetramer analysis and magnetic bead enrichment in 10 patients with acute malaria. EXP1-specific CD4+ T cells were detectable in 9 out of 10 (90%) malaria patients expressing the HLA-DRB1∗11 molecule with an average ex vivo frequency of 0.11% (0-0.22%) of total CD4+ T cells. The phenotype of EXP1-specific CD4+ T cells was further assessed using co-staining with activation (CD38, HLA-DR, CD26), differentiation (CD45RO, CCR7, KLRG1, CD127), senescence (CD57), and co-inhibitory (PD-1, TIGIT, LAG-3, TIM-3) markers as well as the ectonucleotidases CD39 and CD73. EXP1-specific tetramer+ CD4+ T cells had a distinct phenotype compared to bulk CD4+ T cells and displayed a highly activated effector memory phenotype with elevated levels of co-inhibitory receptors and activation markers: EXP1-specific CD4+ T cells universally expressed the co-inhibitory receptors PD-1 and TIGIT as well as the activation marker CD38 and showed elevated frequencies of CD39. These results demonstrate that MHC class II tetramer enrichment is a sensitive approach to investigate ex vivo antigen-specific CD4+ T cells in malaria patients that will aid further analysis of the role of CD4+ T cells during malaria.",
keywords = "CD4-Positive T-Lymphocytes/metabolism, HLA-DR Serological Subtypes, Humans, Malaria, Falciparum, Plasmodium falciparum, Programmed Cell Death 1 Receptor/metabolism, Receptors, Immunologic/metabolism",
author = "Sophia Schulte and Janna Heide and Christin Ackermann and Sven Peine and Michael Ramharter and Mackroth, {Maria Sophia} and Robin Woost and Thomas Jacobs and {Schulze Zur Wiesch}, Julian",
note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2022",
month = apr,
day = "4",
doi = "10.1093/cei/uxab027",
language = "English",
volume = "207",
pages = "227--236",
journal = "CLIN EXP IMMUNOL",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "2",

}

RIS

TY - JOUR

T1 - Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer

AU - Schulte, Sophia

AU - Heide, Janna

AU - Ackermann, Christin

AU - Peine, Sven

AU - Ramharter, Michael

AU - Mackroth, Maria Sophia

AU - Woost, Robin

AU - Jacobs, Thomas

AU - Schulze Zur Wiesch, Julian

N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2022/4/4

Y1 - 2022/4/4

N2 - Relatively little is known about the ex vivo frequency and phenotype of the Plasmodium falciparum-specific CD4+ T-cell response in humans. The exported protein 1 (EXP1) is expressed by plasmodia at both, the liver stage and blood stage, of infection making it a potential target for CD4+ and CD8+ effector T cells. Here, a fluorochrome-labelled HLA-DRB1∗11:01-restriced MHC class II tetramer derived from the P. falciparum EXP1 (aa62-74) was established for ex vivo tetramer analysis and magnetic bead enrichment in 10 patients with acute malaria. EXP1-specific CD4+ T cells were detectable in 9 out of 10 (90%) malaria patients expressing the HLA-DRB1∗11 molecule with an average ex vivo frequency of 0.11% (0-0.22%) of total CD4+ T cells. The phenotype of EXP1-specific CD4+ T cells was further assessed using co-staining with activation (CD38, HLA-DR, CD26), differentiation (CD45RO, CCR7, KLRG1, CD127), senescence (CD57), and co-inhibitory (PD-1, TIGIT, LAG-3, TIM-3) markers as well as the ectonucleotidases CD39 and CD73. EXP1-specific tetramer+ CD4+ T cells had a distinct phenotype compared to bulk CD4+ T cells and displayed a highly activated effector memory phenotype with elevated levels of co-inhibitory receptors and activation markers: EXP1-specific CD4+ T cells universally expressed the co-inhibitory receptors PD-1 and TIGIT as well as the activation marker CD38 and showed elevated frequencies of CD39. These results demonstrate that MHC class II tetramer enrichment is a sensitive approach to investigate ex vivo antigen-specific CD4+ T cells in malaria patients that will aid further analysis of the role of CD4+ T cells during malaria.

AB - Relatively little is known about the ex vivo frequency and phenotype of the Plasmodium falciparum-specific CD4+ T-cell response in humans. The exported protein 1 (EXP1) is expressed by plasmodia at both, the liver stage and blood stage, of infection making it a potential target for CD4+ and CD8+ effector T cells. Here, a fluorochrome-labelled HLA-DRB1∗11:01-restriced MHC class II tetramer derived from the P. falciparum EXP1 (aa62-74) was established for ex vivo tetramer analysis and magnetic bead enrichment in 10 patients with acute malaria. EXP1-specific CD4+ T cells were detectable in 9 out of 10 (90%) malaria patients expressing the HLA-DRB1∗11 molecule with an average ex vivo frequency of 0.11% (0-0.22%) of total CD4+ T cells. The phenotype of EXP1-specific CD4+ T cells was further assessed using co-staining with activation (CD38, HLA-DR, CD26), differentiation (CD45RO, CCR7, KLRG1, CD127), senescence (CD57), and co-inhibitory (PD-1, TIGIT, LAG-3, TIM-3) markers as well as the ectonucleotidases CD39 and CD73. EXP1-specific tetramer+ CD4+ T cells had a distinct phenotype compared to bulk CD4+ T cells and displayed a highly activated effector memory phenotype with elevated levels of co-inhibitory receptors and activation markers: EXP1-specific CD4+ T cells universally expressed the co-inhibitory receptors PD-1 and TIGIT as well as the activation marker CD38 and showed elevated frequencies of CD39. These results demonstrate that MHC class II tetramer enrichment is a sensitive approach to investigate ex vivo antigen-specific CD4+ T cells in malaria patients that will aid further analysis of the role of CD4+ T cells during malaria.

KW - CD4-Positive T-Lymphocytes/metabolism

KW - HLA-DR Serological Subtypes

KW - Humans

KW - Malaria, Falciparum

KW - Plasmodium falciparum

KW - Programmed Cell Death 1 Receptor/metabolism

KW - Receptors, Immunologic/metabolism

U2 - 10.1093/cei/uxab027

DO - 10.1093/cei/uxab027

M3 - SCORING: Journal article

C2 - 35020841

VL - 207

SP - 227

EP - 236

JO - CLIN EXP IMMUNOL

JF - CLIN EXP IMMUNOL

SN - 0009-9104

IS - 2

ER -