Dominant TNF-α+ Mycobacterium Tuberculosis-Specific CD4+ T Cell Responses Discriminate Between Latent Infection and Active Disease

Nat Med. 2011 Mar;17(3):372-6. doi: 10.1038/nm.2299. Epub 2011 Feb 20.

Abstract

Rapid diagnosis of active Mycobacterium tuberculosis (Mtb) infection remains a clinical and laboratory challenge. We have analyzed the cytokine profile (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2)) of Mtb-specific T cells by polychromatic flow cytometry. We studied Mtb-specific CD4+ T cell responses in subjects with latent Mtb infection and active tuberculosis disease. The results showed substantial increase in the proportion of single-positive TNF-α Mtb-specific CD4+ T cells in subjects with active disease, and this parameter was the strongest predictor of diagnosis of active disease versus latent infection. We validated the use of this parameter in a cohort of 101 subjects with tuberculosis diagnosis unknown to the investigator. The sensitivity and specificity of the flow cytometry-based assay were 67% and 92%, respectively, the positive predictive value was 80% and the negative predictive value was 92.4%. Therefore, the proportion of single-positive TNF-α Mtb-specific CD4+ T cells is a new tool for the rapid diagnosis of active tuberculosis disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis / immunology*
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Tumor Necrosis Factor-alpha