Mycobacterium tuberculosis‐specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease

Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb‐specific CD8+ T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb‐specific CD8+ T cells in 326 subjects with latent Mtb infection (LTBI) or active T...

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Published inEuropean journal of immunology Vol. 43; no. 6; pp. 1568 - 1577
Main Authors Rozot, Virginie, Vigano, Selena, Mazza‐Stalder, Jesica, Idrizi, Elita, Day, Cheryl L., Perreau, Matthieu, Lazor‐Blanchet, Catherine, Petruccioli, Elisa, Hanekom, Willem, Goletti, Delia, Bart, Pierre‐Alexandre, Nicod, Laurent, Pantaleo, Giuseppe, Harari, Alexandre
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 01.06.2013
Subjects
Active TB disease
Acute Disease
Antigens, CD - metabolism
CD8-Positive T-Lymphocytes - immunology
Cell Proliferation
Cells, Cultured
Cytokines - metabolism
Cytotoxicity
Functional profile
GPI-Linked Proteins - metabolism
Humans
Immunology
Immunophenotyping
Latent Mtb infection
Latent Tuberculosis - immunology
Lymphocytes
Mtb‐specific CD8+ T cells
Mycobacterium tuberculosis - immunology
Programmed Cell Death 1 Receptor - metabolism
Receptors, Immunologic - metabolism
Signaling Lymphocytic Activation Molecule Family
T cell receptors
T-Lymphocyte Subsets - immunology
Tuberculosis
Tuberculosis, Pulmonary - immunology
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Abstract Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb‐specific CD8+ T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb‐specific CD8+ T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb‐specific CD8+ T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb‐specific CD8+ T cells in LTBI subjects were mostly TEMRA cells (CD45RA+CCR7−), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA−CCR7−), expressing 2B4 but lacking PD‐1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb‐specific CD8+ T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro‐expanded Mtb‐specific CD8+ T cells expressed perforin and granulysin. Finally, Mtb‐specific CD8+ T‐cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb‐specific CD8+ T‐cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb‐specific CD8+ T‐cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
AbstractList Protective immunity to Mycobacterium tuberculosis ( Mtb ) remains poorly understood and the role of Mtb ‐specific CD8 + T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb ‐specific CD8 + T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb ‐specific CD8 + T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb ‐specific CD8 + T cells in LTBI subjects were mostly T EMRA cells (CD45RA + CCR7 − ), coexpressing 2B4 and CD160, and in TB patients were mostly T EM cells (CD45RA − CCR7 − ), expressing 2B4 but lacking PD‐1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb ‐specific CD8 + T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro‐expanded Mtb ‐specific CD8 + T cells expressed perforin and granulysin. Finally, Mtb ‐specific CD8 + T‐cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb ‐specific CD8 + T‐cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb ‐specific CD8 + T‐cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb‐specific CD8+ T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb‐specific CD8+ T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb‐specific CD8+ T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb‐specific CD8+ T cells in LTBI subjects were mostly TEMRA cells (CD45RA+CCR7−), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA−CCR7−), expressing 2B4 but lacking PD‐1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb‐specific CD8+ T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro‐expanded Mtb‐specific CD8+ T cells expressed perforin and granulysin. Finally, Mtb‐specific CD8+ T‐cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb‐specific CD8+ T‐cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb‐specific CD8+ T‐cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8+ T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8+ T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8+ T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8+ T cells in LTBI subjects were mostly TEMRA cells (CD45RA+CCR7-), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA-CCR7-), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8+ T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8+ T cells expressed perforin and granulysin. Finally, Mtb-specific CD8+ T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8+ T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8+ T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response. [PUBLICATION ABSTRACT]
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8(+) T cells in LTBI subjects were mostly T EMRA cells (CD45RA(+) CCR7(-)), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA(-) CCR7(-)), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8(+) T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8(+) T cells in LTBI subjects were mostly T EMRA cells (CD45RA(+) CCR7(-)), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA(-) CCR7(-)), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8(+) T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8(+) T cells in LTBI subjects were mostly T EMRA cells (CD45RA(+) CCR7(-)), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA(-) CCR7(-)), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8(+) T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
Author Nicod, Laurent
Idrizi, Elita
Petruccioli, Elisa
Mazza‐Stalder, Jesica
Bart, Pierre‐Alexandre
Rozot, Virginie
Day, Cheryl L.
Perreau, Matthieu
Pantaleo, Giuseppe
Lazor‐Blanchet, Catherine
Hanekom, Willem
Goletti, Delia
Harari, Alexandre
Vigano, Selena
AuthorAffiliation 3 South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
1 Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
4 Division of Occupational Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
5 National Institute for Infectious Diseases, Rome, Italy
2 Division of Pneumology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
6 Swiss Vaccine Research Institute, Lausanne, Switzerland
AuthorAffiliation_xml – name: 2 Division of Pneumology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
– name: 4 Division of Occupational Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
– name: 5 National Institute for Infectious Diseases, Rome, Italy
– name: 3 South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa
– name: 1 Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
– name: 6 Swiss Vaccine Research Institute, Lausanne, Switzerland
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  surname: Rozot
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  organization: University of Lausanne
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  organization: University of Cape Town
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  fullname: Perreau, Matthieu
  organization: University of Lausanne
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  fullname: Petruccioli, Elisa
  organization: National Institute for Infectious Diseases
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  fullname: Hanekom, Willem
  organization: University of Cape Town
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  organization: National Institute for Infectious Diseases
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  organization: University of Lausanne
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  surname: Nicod
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  organization: University of Lausanne
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/23456989$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Copyright_xml – notice: 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
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Snippet Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb‐specific CD8+ T cells is controversial. Here we performed...
Protective immunity to Mycobacterium tuberculosis ( Mtb ) remains poorly understood and the role of Mtb ‐specific CD8 + T cells is controversial. Here we...
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we...
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8+ T cells is controversial. Here we performed...
Protective immunity to Mycobacterium tuberculosis ( Mtb ) remains poorly understood and the role of Mtb -specific CD8 + T cells is controversial. Here we...
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SubjectTerms Active TB disease
Acute Disease
Antigens, CD - metabolism
CD8-Positive T-Lymphocytes - immunology
Cell Proliferation
Cells, Cultured
Cytokines - metabolism
Cytotoxicity
Functional profile
GPI-Linked Proteins - metabolism
Humans
Immunology
Immunophenotyping
Latent Mtb infection
Latent Tuberculosis - immunology
Lymphocytes
Mtb‐specific CD8+ T cells
Mycobacterium tuberculosis - immunology
Programmed Cell Death 1 Receptor - metabolism
Receptors, Immunologic - metabolism
Signaling Lymphocytic Activation Molecule Family
T cell receptors
T-Lymphocyte Subsets - immunology
Tuberculosis
Tuberculosis, Pulmonary - immunology
Title Mycobacterium tuberculosis‐specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Feji.201243262
https://www.ncbi.nlm.nih.gov/pubmed/23456989
https://www.proquest.com/docview/1370047363
https://www.proquest.com/docview/1370638625
https://pubmed.ncbi.nlm.nih.gov/PMC6535091
Volume 43
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