Analysis of Mycobacterium tuberculosis-specific CD8 T-cells in patients with active tuberculosis and in individuals with latent infection

Nadia Rosalia Caccamo, Alfredo Salerno, Francesco Dieli, Lucina Titone Lanza Di Scalea, Paola Di Carlo, Serena Meraviglia, Giuliana Guggino, Giuseppe Gelsomino, Jan Nouta, Marialuisa Bocchino, Alessandro Sanduzzi, Tom H.M. Ottenhoff, Alessandro Matarese, Michel R. Klein, Domenico Galati

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Abstract

CD8 T-cells contribute to control of Mycobacterium tuberculosis infection, but little is known about the quality of the CD8 T-cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopes from 6 different proteins of Mycobacterium tuberculosis were detected by tetramer staining. Intracellular cytokines staining for specific production of IFN-gamma and IL-2 was performed, complemented by phenotyping of memory markers on antigen-specific CD8 T-cells. The ex-vivo frequencies of tetramer-specific CD8 T-cells in tuberculous patients before therapy were lower than in subjects with latent infection, but increased at four months after therapy to comparable percentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR7(-)). In contrast, tuberculous patients had only 35% of antigen-specific CD8 T-cells expressing this phenotype, while containing higher proportions of cells with an effector memory- and a central memory-like phenotype, and which did not change significantly after therapy. CD8 T-cells from subjects with latent infection showed a codominance of IL-2+/IFN-gamma+ and IL-2(-)/IFN-gamma+ T-cell populations; interestingly, only the IL-2+/IFN-gamma+ population was reduced or absent in tuberculous patients, highly suggestive of a restricted functional profile of Mycobacterium tuberculosis-specific CD8 T-cells during active disease. These results suggest distinct Mycobacterium tuberculosis specific CD8 T-cell phenotypic and functional signatures between subjects which control infection (subjects with latent infection) and those who do not (patients with active disease).
Lingua originaleEnglish
pagine (da-a)-
Numero di pagine0
RivistaPLoS One
Volume4
Stato di pubblicazionePublished - 2009

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T-cells
Mycobacterium tuberculosis
tuberculosis
Inpatients
Tuberculosis
T-lymphocytes
T-Lymphocytes
Infection
infection
interleukin-2
Interleukin-2
phenotype
Phenotype
Data storage equipment
therapeutics
Staining and Labeling
CD8 Antigens
codominance
antigens
Mycobacterium Infections

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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title = "Analysis of Mycobacterium tuberculosis-specific CD8 T-cells in patients with active tuberculosis and in individuals with latent infection",
abstract = "CD8 T-cells contribute to control of Mycobacterium tuberculosis infection, but little is known about the quality of the CD8 T-cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopes from 6 different proteins of Mycobacterium tuberculosis were detected by tetramer staining. Intracellular cytokines staining for specific production of IFN-gamma and IL-2 was performed, complemented by phenotyping of memory markers on antigen-specific CD8 T-cells. The ex-vivo frequencies of tetramer-specific CD8 T-cells in tuberculous patients before therapy were lower than in subjects with latent infection, but increased at four months after therapy to comparable percentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR7(-)). In contrast, tuberculous patients had only 35{\%} of antigen-specific CD8 T-cells expressing this phenotype, while containing higher proportions of cells with an effector memory- and a central memory-like phenotype, and which did not change significantly after therapy. CD8 T-cells from subjects with latent infection showed a codominance of IL-2+/IFN-gamma+ and IL-2(-)/IFN-gamma+ T-cell populations; interestingly, only the IL-2+/IFN-gamma+ population was reduced or absent in tuberculous patients, highly suggestive of a restricted functional profile of Mycobacterium tuberculosis-specific CD8 T-cells during active disease. These results suggest distinct Mycobacterium tuberculosis specific CD8 T-cell phenotypic and functional signatures between subjects which control infection (subjects with latent infection) and those who do not (patients with active disease).",
keywords = "Mycobacterium tuberculosis, CD8 T cells, Tuberculosis, Latent Infection",
author = "Caccamo, {Nadia Rosalia} and Alfredo Salerno and Francesco Dieli and {Titone Lanza Di Scalea}, Lucina and {Di Carlo}, Paola and Serena Meraviglia and Giuliana Guggino and Giuseppe Gelsomino and Jan Nouta and Marialuisa Bocchino and Alessandro Sanduzzi and Ottenhoff, {Tom H.M.} and Alessandro Matarese and Klein, {Michel R.} and Domenico Galati",
year = "2009",
language = "English",
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journal = "PLoS One",
issn = "1932-6203",
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TY - JOUR

T1 - Analysis of Mycobacterium tuberculosis-specific CD8 T-cells in patients with active tuberculosis and in individuals with latent infection

AU - Caccamo, Nadia Rosalia

AU - Salerno, Alfredo

AU - Dieli, Francesco

AU - Titone Lanza Di Scalea, Lucina

AU - Di Carlo, Paola

AU - Meraviglia, Serena

AU - Guggino, Giuliana

AU - Gelsomino, Giuseppe

AU - Nouta, Jan

AU - Bocchino, Marialuisa

AU - Sanduzzi, Alessandro

AU - Ottenhoff, Tom H.M.

AU - Matarese, Alessandro

AU - Klein, Michel R.

AU - Galati, Domenico

PY - 2009

Y1 - 2009

N2 - CD8 T-cells contribute to control of Mycobacterium tuberculosis infection, but little is known about the quality of the CD8 T-cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopes from 6 different proteins of Mycobacterium tuberculosis were detected by tetramer staining. Intracellular cytokines staining for specific production of IFN-gamma and IL-2 was performed, complemented by phenotyping of memory markers on antigen-specific CD8 T-cells. The ex-vivo frequencies of tetramer-specific CD8 T-cells in tuberculous patients before therapy were lower than in subjects with latent infection, but increased at four months after therapy to comparable percentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR7(-)). In contrast, tuberculous patients had only 35% of antigen-specific CD8 T-cells expressing this phenotype, while containing higher proportions of cells with an effector memory- and a central memory-like phenotype, and which did not change significantly after therapy. CD8 T-cells from subjects with latent infection showed a codominance of IL-2+/IFN-gamma+ and IL-2(-)/IFN-gamma+ T-cell populations; interestingly, only the IL-2+/IFN-gamma+ population was reduced or absent in tuberculous patients, highly suggestive of a restricted functional profile of Mycobacterium tuberculosis-specific CD8 T-cells during active disease. These results suggest distinct Mycobacterium tuberculosis specific CD8 T-cell phenotypic and functional signatures between subjects which control infection (subjects with latent infection) and those who do not (patients with active disease).

AB - CD8 T-cells contribute to control of Mycobacterium tuberculosis infection, but little is known about the quality of the CD8 T-cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopes from 6 different proteins of Mycobacterium tuberculosis were detected by tetramer staining. Intracellular cytokines staining for specific production of IFN-gamma and IL-2 was performed, complemented by phenotyping of memory markers on antigen-specific CD8 T-cells. The ex-vivo frequencies of tetramer-specific CD8 T-cells in tuberculous patients before therapy were lower than in subjects with latent infection, but increased at four months after therapy to comparable percentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR7(-)). In contrast, tuberculous patients had only 35% of antigen-specific CD8 T-cells expressing this phenotype, while containing higher proportions of cells with an effector memory- and a central memory-like phenotype, and which did not change significantly after therapy. CD8 T-cells from subjects with latent infection showed a codominance of IL-2+/IFN-gamma+ and IL-2(-)/IFN-gamma+ T-cell populations; interestingly, only the IL-2+/IFN-gamma+ population was reduced or absent in tuberculous patients, highly suggestive of a restricted functional profile of Mycobacterium tuberculosis-specific CD8 T-cells during active disease. These results suggest distinct Mycobacterium tuberculosis specific CD8 T-cell phenotypic and functional signatures between subjects which control infection (subjects with latent infection) and those who do not (patients with active disease).

KW - Mycobacterium tuberculosis, CD8 T cells, Tuberculosis, Latent Infection

UR - http://hdl.handle.net/10447/37799

M3 - Article

VL - 4

SP - -

JO - PLoS One

JF - PLoS One

SN - 1932-6203

ER -