Expanded Polyfunctional T Cell Response to Mycobacterial Antigens in TB Disease and Contraction Post-Treatment

PLoS One. 2010 Jun 21;5(6):e11237. doi: 10.1371/journal.pone.0011237.

Abstract

Background: T cells producing multiple factors have been shown to be required for protection from disease progression in HIV but we have recently shown this not to be the case in TB. Subjects with active disease had a greater proportion of polyfunctional cells responding to ESAT-6/CFP-10 stimulation than their infected but non-diseased household contacts (HHC). We therefore wanted to assess this profile in subjects who had successfully completed standard TB chemotherapy.

Methods: We performed a cross-sectional study using PBMC from TB cases (pre- and post-treatment) and HHC. Samples were stimulated overnight with TB antigens (ESAT-6/CFP-10 and PPD) and their CD4+ and CD8+ T cells were assessed for production of CD107a, IFN-gamma, IL-2 and TNF-alpha and the complexity of the responses was determined using SPICE and PESTLE software.

Results and conclusions: We found that an increase in complexity (i.e., production of more than 1 factor simultaneously) of the T cell profile was associated with TB disease and that this was significantly reduced following TB treatment. This implies that T cells are able to respond adequately to TB antigens with active disease (at least initially) but the ability of this response to protect the host from disease progression is hampered, presumably due to immune evasion strategies by the bacteria. These findings have implications for the development of new diagnostics and vaccine strategies.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, Bacterial / immunology*
  • Bacterial Vaccines / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Lysosomal-Associated Membrane Protein 1 / biosynthesis
  • Mycobacterium tuberculosis / immunology*
  • Species Specificity
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / microbiology
  • Tuberculosis / diagnosis
  • Tuberculosis / immunology*
  • Tuberculosis / therapy*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antigens, Bacterial
  • Bacterial Vaccines
  • Interleukin-2
  • Lysosomal-Associated Membrane Protein 1
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma