KLRG1 and PD-1 expression are increased on T-cells following tuberculosis-treatment and identify cells with different proliferative capacities in BCG-vaccinated adults

Mardi C. Boer, Krista E. Van Meijgaarden, Delia Goletti, Valentina Vanini, Corine Prins, Tom H M Ottenhoff, Simone A. Joosten

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Summary In cancer and chronic infectious diseases, immune checkpoint-blockade of inhibitory receptors can enhance T-cell immunity. In tuberculosis (TB), a chronic infectious disease, prolonged antigen exposure can potentially drive terminal T-cell differentiation towards functional 'exhaustion': in human TB T-cells express PD-1 (programmed cell death protein-1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein-4). However, in murine TB not PD-1 but rather killer cell lectin-like receptor subfamily-G1 (KLRG1) was a superior indicator of terminal T-cell differentiation. We therefore compared expression of KLRG1, PD-1 and CTLA-4 on T-cells in different stages of human TB, and also analysed their induction following BCG-vaccination. KLRG1, PD-1 and CTLA-4-expression were highest on in vitro BCG-stimulated CD4+ T-cells following recent TB-treatment; KLRG1 and PD-1-expression on CD4+ T-cells in active - but not latent - TB were only slightly increased compared to healthy donors. BCG-vaccination induced KLRG1-expression on BCG-stimulated CD8+ but not CD4+ T-cells, while neither PD-1 nor CTLA-4-expression increased. KLRG1-expressing CD8+ T-cells exhibited markedly decreased proliferation, whereas PD-1+ T-cells proliferated after in vitro BCG-stimulation. Thus, we demonstrate the presence of increased KLRG1-expressing T-cells in TB-treated individuals, and present KLRG1 as a marker of decreased human T-cell proliferation following BCG-vaccination. These results expand our understanding of cell-mediated immune control of mycobacterial infections.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalTuberculosis
Volume97
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

NK Cell Lectin-Like Receptors
Programmed Cell Death 1 Receptor
Mycobacterium bovis
Tuberculosis
T-Lymphocytes
Cytotoxic T-Lymphocytes
Therapeutics
Vaccination
Communicable Diseases
Cell Differentiation
Proteins
Chronic Disease
Latent Tuberculosis

Keywords

  • BCG-vaccination
  • CTLA-4
  • Human T-cells
  • Immune checkpoint-blockade
  • Immunity
  • Inhibitory receptors
  • KLRG1
  • PD-1
  • T-cell exhaustion
  • T-cells
  • Terminal differentiation
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases
  • Microbiology (medical)

Cite this

KLRG1 and PD-1 expression are increased on T-cells following tuberculosis-treatment and identify cells with different proliferative capacities in BCG-vaccinated adults. / Boer, Mardi C.; Van Meijgaarden, Krista E.; Goletti, Delia; Vanini, Valentina; Prins, Corine; Ottenhoff, Tom H M; Joosten, Simone A.

In: Tuberculosis, Vol. 97, 01.03.2016, p. 163-171.

Research output: Contribution to journalArticle

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abstract = "Summary In cancer and chronic infectious diseases, immune checkpoint-blockade of inhibitory receptors can enhance T-cell immunity. In tuberculosis (TB), a chronic infectious disease, prolonged antigen exposure can potentially drive terminal T-cell differentiation towards functional 'exhaustion': in human TB T-cells express PD-1 (programmed cell death protein-1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein-4). However, in murine TB not PD-1 but rather killer cell lectin-like receptor subfamily-G1 (KLRG1) was a superior indicator of terminal T-cell differentiation. We therefore compared expression of KLRG1, PD-1 and CTLA-4 on T-cells in different stages of human TB, and also analysed their induction following BCG-vaccination. KLRG1, PD-1 and CTLA-4-expression were highest on in vitro BCG-stimulated CD4+ T-cells following recent TB-treatment; KLRG1 and PD-1-expression on CD4+ T-cells in active - but not latent - TB were only slightly increased compared to healthy donors. BCG-vaccination induced KLRG1-expression on BCG-stimulated CD8+ but not CD4+ T-cells, while neither PD-1 nor CTLA-4-expression increased. KLRG1-expressing CD8+ T-cells exhibited markedly decreased proliferation, whereas PD-1+ T-cells proliferated after in vitro BCG-stimulation. Thus, we demonstrate the presence of increased KLRG1-expressing T-cells in TB-treated individuals, and present KLRG1 as a marker of decreased human T-cell proliferation following BCG-vaccination. These results expand our understanding of cell-mediated immune control of mycobacterial infections.",
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AU - Boer, Mardi C.

AU - Van Meijgaarden, Krista E.

AU - Goletti, Delia

AU - Vanini, Valentina

AU - Prins, Corine

AU - Ottenhoff, Tom H M

AU - Joosten, Simone A.

PY - 2016/3/1

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N2 - Summary In cancer and chronic infectious diseases, immune checkpoint-blockade of inhibitory receptors can enhance T-cell immunity. In tuberculosis (TB), a chronic infectious disease, prolonged antigen exposure can potentially drive terminal T-cell differentiation towards functional 'exhaustion': in human TB T-cells express PD-1 (programmed cell death protein-1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein-4). However, in murine TB not PD-1 but rather killer cell lectin-like receptor subfamily-G1 (KLRG1) was a superior indicator of terminal T-cell differentiation. We therefore compared expression of KLRG1, PD-1 and CTLA-4 on T-cells in different stages of human TB, and also analysed their induction following BCG-vaccination. KLRG1, PD-1 and CTLA-4-expression were highest on in vitro BCG-stimulated CD4+ T-cells following recent TB-treatment; KLRG1 and PD-1-expression on CD4+ T-cells in active - but not latent - TB were only slightly increased compared to healthy donors. BCG-vaccination induced KLRG1-expression on BCG-stimulated CD8+ but not CD4+ T-cells, while neither PD-1 nor CTLA-4-expression increased. KLRG1-expressing CD8+ T-cells exhibited markedly decreased proliferation, whereas PD-1+ T-cells proliferated after in vitro BCG-stimulation. Thus, we demonstrate the presence of increased KLRG1-expressing T-cells in TB-treated individuals, and present KLRG1 as a marker of decreased human T-cell proliferation following BCG-vaccination. These results expand our understanding of cell-mediated immune control of mycobacterial infections.

AB - Summary In cancer and chronic infectious diseases, immune checkpoint-blockade of inhibitory receptors can enhance T-cell immunity. In tuberculosis (TB), a chronic infectious disease, prolonged antigen exposure can potentially drive terminal T-cell differentiation towards functional 'exhaustion': in human TB T-cells express PD-1 (programmed cell death protein-1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein-4). However, in murine TB not PD-1 but rather killer cell lectin-like receptor subfamily-G1 (KLRG1) was a superior indicator of terminal T-cell differentiation. We therefore compared expression of KLRG1, PD-1 and CTLA-4 on T-cells in different stages of human TB, and also analysed their induction following BCG-vaccination. KLRG1, PD-1 and CTLA-4-expression were highest on in vitro BCG-stimulated CD4+ T-cells following recent TB-treatment; KLRG1 and PD-1-expression on CD4+ T-cells in active - but not latent - TB were only slightly increased compared to healthy donors. BCG-vaccination induced KLRG1-expression on BCG-stimulated CD8+ but not CD4+ T-cells, while neither PD-1 nor CTLA-4-expression increased. KLRG1-expressing CD8+ T-cells exhibited markedly decreased proliferation, whereas PD-1+ T-cells proliferated after in vitro BCG-stimulation. Thus, we demonstrate the presence of increased KLRG1-expressing T-cells in TB-treated individuals, and present KLRG1 as a marker of decreased human T-cell proliferation following BCG-vaccination. These results expand our understanding of cell-mediated immune control of mycobacterial infections.

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KW - Inhibitory receptors

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KW - T-cell exhaustion

KW - T-cells

KW - Terminal differentiation

KW - Tuberculosis

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