Lack of Mycobacterium tuberculosis–specific interleukin‐17A–producing CD4+ T cells in active disease. Issue 4 (6th March 2013)

• Record Type: Journal Article
• Authors: Perreau, Matthieu; Rozot, Virginie; Welles, Hugh C.; Belluti‐Enders, Felicitas; Vigano, Selena; Maillard, Michel; Dorta, Gian; Mazza‐Stalder, Jesica; Bart, Pierre‐Alexandre; Roger, Thierry; Calandra, Thierry; Nicod, Laurent; Harari, Alexandre
• Is Part Of: European journal of immunology. Volume 43:Issue 4(2013:Apr.)
• Page Start: 939
• Page End: 948
• Publication Date: 2013-03-06
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201243090
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Protective immunity to <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb)</italic> is commonly ascribed to a Th1 profile; however, the involvement of Th17 cells remains to be clarified. Here, we characterized <italic>Mtb</italic>‐specific CD4<sup>+</sup> T cells in blood and bronchoalveolar lavages (BALs) from untreated subjects with either active tuberculosis disease (TB) or latent <italic>Mtb</italic> infection (LTBI), considered as prototypic models of uncontrolled or controlled infection, respectively. The production of IL‐17A, IFN‐γ, TNF‐α, and IL‐2 by <italic>Mtb</italic>‐specific CD4<sup>+</sup> T cells was assessed both directly ex vivo and following in vitro antigen‐specific T‐cell expansion. Unlike for extracellular bacteria, <italic>Mtb</italic>‐specific CD4<sup>+</sup> T‐cell responses lacked immediate ex vivo IL‐17A effector function in both LTBI and TB individuals. Furthermore, <italic>Mtb</italic>‐specific Th17 cells were absent in BALs, while extracellular bacteria‐specific Th17 cells were identified in gut biopsies of healthy individuals. Interestingly, only <italic>Mtb</italic>‐specific CD4<sup>+</sup> T cells from 50% of LTBI but not from TB subjects acquired the ability to produce IL‐17A following <italic>Mtb</italic>‐specific T‐cell expansion. Finally, IL‐17A acquisition by <italic>Mtb</italic>‐specific CD4<sup>+</sup> T cells correlated with the coexpression of CXCR3 and CCR6, currently associated to Th1 or Th17 profiles, respectively. Our data demonstrate that <italic>Mtb</italic>‐specific Th17 cells are selectively undetectable in peripheral blood and BALs from TB patients.</p> </abstract>