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

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

Research output: Contribution to journalArticle

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-γ 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 -γ+ and IL-2-/IFN-γ+ T-cell populations; interestingly, only the IL-2+/IFN- γ+ 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).

Original languageEnglish
Article numbere5528
JournalPLoS One
Volume4
Issue number5
DOIs
Publication statusPublished - May 13 2009

ASJC Scopus subject areas

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

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    Caccamo, N., Guggino, G., Meraviglia, S., Gelsomino, G., Di Carlo, P., Titone, L., Bocchino, M., Galati, D., Matarese, A., Nouta, J., Klein, M. R., Salerno, A., Sanduzzi, A., Dieli, F., & Ottenhoff, T. H. M. (2009). Analysis of Mycobacterium tuberculosis-specific CD8 T-cells in patients with active tuberculosis and in individuals with latent infection. PLoS One, 4(5), [e5528]. https://doi.org/10.1371/journal.pone.0005528