Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+TÂ cells

Nadia Rosalia Caccamo, Teresa Prezzemolo, Francesco Dieli, Teresa Prezzemolo, Simone A. Joosten, Krista E. Van Meijgaarden, Kees L.M.C. Franken, Tom H.M. Ottenhoff

Risultato della ricerca: Article

10 Citazioni (Scopus)

Abstract

HLA-E presented antigens are interesting targets for vaccination given HLA-Esâ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8+effector T cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb-peptide/HLA-E-TM+CD8+T cells in the circulation of patients with active tuberculosis (TB). HLA-E restricted CD8+T cells from TB patients produced more IL-13 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8+T cells, HLA-E restricted cells produced more IFNγ, IL-4, IL-10, and granulysin but less granzyme-A. Moreover, compared to âclassicalâ Mtb specific HLA-A2 restricted CD8+T cells, HLA-E restricted CD8+T cells produced less TNFα and perforin, but more IL-4. In conclusion, HLA-E restricted- Mtb specific cells can produce Th2 cytokines directly.
Lingua originaleEnglish
pagine (da-a)293-305
Numero di pagine13
RivistaEuropean Journal of Immunology
Volume48
Stato di pubblicazionePublished - 2018

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Mycobacterium tuberculosis
T-Lymphocytes
Interleukin-4
Tuberculosis
Cytokines
Latent Tuberculosis
HLA-A2 Antigen
Granzymes
Perforin
Interleukin-13
Interleukin-10
Vaccination
Transcription Factors
Staining and Labeling
Phenotype
Peptides

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cita questo

Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+TÂ cells. / Caccamo, Nadia Rosalia; Prezzemolo, Teresa; Dieli, Francesco; Prezzemolo, Teresa; Joosten, Simone A.; Van Meijgaarden, Krista E.; Franken, Kees L.M.C.; Ottenhoff, Tom H.M.

In: European Journal of Immunology, Vol. 48, 2018, pag. 293-305.

Risultato della ricerca: Article

Caccamo, NR, Prezzemolo, T, Dieli, F, Prezzemolo, T, Joosten, SA, Van Meijgaarden, KE, Franken, KLMC & Ottenhoff, THM 2018, 'Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+TÂ cells', European Journal of Immunology, vol. 48, pagg. 293-305.
Caccamo, Nadia Rosalia ; Prezzemolo, Teresa ; Dieli, Francesco ; Prezzemolo, Teresa ; Joosten, Simone A. ; Van Meijgaarden, Krista E. ; Franken, Kees L.M.C. ; Ottenhoff, Tom H.M. / Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+TÂ cells. In: European Journal of Immunology. 2018 ; Vol. 48. pagg. 293-305.
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abstract = "HLA-E presented antigens are interesting targets for vaccination given HLA-Es{\^a} essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8+effector T{\^A} cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb-peptide/HLA-E-TM+CD8+T{\^A} cells in the circulation of patients with active tuberculosis (TB). HLA-E restricted CD8+T{\^A} cells from TB patients produced more IL-13 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8+T{\^A} cells, HLA-E restricted cells produced more IFN{\^I}³, IL-4, IL-10, and granulysin but less granzyme-A. Moreover, compared to {\^a}classical{\^a} Mtb specific HLA-A2 restricted CD8+T{\^A} cells, HLA-E restricted CD8+T{\^A} cells produced less TNF{\^I}± and perforin, but more IL-4. In conclusion, HLA-E restricted- Mtb specific cells can produce Th2 cytokines directly.",
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AU - Prezzemolo, Teresa

AU - Dieli, Francesco

AU - Prezzemolo, Teresa

AU - Joosten, Simone A.

AU - Van Meijgaarden, Krista E.

AU - Franken, Kees L.M.C.

AU - Ottenhoff, Tom H.M.

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N2 - HLA-E presented antigens are interesting targets for vaccination given HLA-Esâ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8+effector T cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb-peptide/HLA-E-TM+CD8+T cells in the circulation of patients with active tuberculosis (TB). HLA-E restricted CD8+T cells from TB patients produced more IL-13 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8+T cells, HLA-E restricted cells produced more IFNγ, IL-4, IL-10, and granulysin but less granzyme-A. Moreover, compared to âclassicalâ Mtb specific HLA-A2 restricted CD8+T cells, HLA-E restricted CD8+T cells produced less TNFα and perforin, but more IL-4. In conclusion, HLA-E restricted- Mtb specific cells can produce Th2 cytokines directly.

AB - HLA-E presented antigens are interesting targets for vaccination given HLA-Esâ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8+effector T cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb-peptide/HLA-E-TM+CD8+T cells in the circulation of patients with active tuberculosis (TB). HLA-E restricted CD8+T cells from TB patients produced more IL-13 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8+T cells, HLA-E restricted cells produced more IFNγ, IL-4, IL-10, and granulysin but less granzyme-A. Moreover, compared to âclassicalâ Mtb specific HLA-A2 restricted CD8+T cells, HLA-E restricted CD8+T cells produced less TNFα and perforin, but more IL-4. In conclusion, HLA-E restricted- Mtb specific cells can produce Th2 cytokines directly.

KW - Active TB

KW - CD8+T cells

KW - Cytokines

KW - Immunology

KW - Immunology and Allergy

KW - Tetramers

KW - Th2

UR - http://hdl.handle.net/10447/273877

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