Mycobacterium Tuberculosis-Specific CD8+ T Cells Are Functionally and Phenotypically Different Between Latent Infection and Active Disease

Eur J Immunol. 2013 Jun;43(6):1568-77. doi: 10.1002/eji.201243262.

Abstract

Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8(+) T cells in LTBI subjects were mostly T EMRA cells (CD45RA(+) CCR7(-)), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA(-) CCR7(-)), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8(+) T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Antigens, CD / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunophenotyping
  • Latent Tuberculosis / immunology*
  • Mycobacterium tuberculosis / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptors, Immunologic / metabolism
  • Signaling Lymphocytic Activation Molecule Family
  • T-Lymphocyte Subsets / immunology*
  • Tuberculosis, Pulmonary / immunology*

Substances

  • Antigens, CD
  • CD160 protein, human
  • CD244 protein, human
  • Cytokines
  • GPI-Linked Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • Signaling Lymphocytic Activation Molecule Family