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

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

Risultato della ricerca: Article

81 Citazioni (Scopus)

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
Numero di pagine0
RivistaPLoS One
Volume4
Stato di pubblicazionePublished - 2009

All Science Journal Classification (ASJC) codes

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

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