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MARCO PIO LA MANNA

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines

  • Autori: Caccamo, N.; Pietra, G.; Sullivan, L.; Brooks, A.; Prezzemolo, T.; La Manna, M.; Di liberto, D.; Joosten, S.; van Meijgaarden, K.; Di Carlo, P.; Titone, L.; Moretta, L.; Mingari, M.; Ottenhoff, T.; Dieli, F.
  • Anno di pubblicazione: 2015
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/127531

Abstract

CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.