Immunosuppression During Active Tuberculosis Is Characterized by Decreased Interferon- Gamma Production and CD25 Expression With Elevated Forkhead Box P3, Transforming Growth Factor- Beta , and interleukin-4 mRNA Levels

J Infect Dis. 2007 Mar 15;195(6):870-8. doi: 10.1086/511277. Epub 2007 Feb 1.

Abstract

The balance between effector and regulatory responses after Mycobacterium tuberculosis infection may dictate outcome and progression to active disease. We investigated effector and regulatory T cell responses in bacille Calmette-Guerin (BCG)-stimulated peripheral blood mononuclear cells and whole blood cultures from persons with active tuberculosis (TB), persons with TB at the end of 6 months of treatment, and healthy control subjects with latent TB infection. All 3 groups displayed BCG-induced increases in effector and regulatory T cell phenotypes as defined by CD4(+)CD25(lo) and CD4(+)CD25(hi) T cells, respectively. In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4(+)CD25(hi), CTLA-4, and interferon- gamma . However, these case patients expressed the highest mRNA levels of forkhead box P3, transforming growth factor (TGF)- beta , and interleukin (IL)-4 and a lower T-bet : GATA-3 ratio. There were no significant differences in IL-4 delta 2, IL-10, or TGF- beta receptor-II mRNA expression between groups. Together, these results suggest that immunosuppression seen after mycobacterial stimulation in case patients with active TB is associated with naturally occurring regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / blood
  • Antigens, CD / genetics
  • BCG Vaccine
  • CD3 Complex / genetics
  • CD4 Lymphocyte Count
  • DNA Primers
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation
  • Humans
  • Immunosuppression
  • Interferon-gamma / genetics*
  • Interleukin-2 Receptor alpha Subunit / genetics*
  • Interleukin-4 / genetics*
  • Lymphocyte Count
  • Mycobacterium tuberculosis
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics*
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta / genetics
  • Tuberculosis / immunology*

Substances

  • Antigens, CD
  • BCG Vaccine
  • CD3 Complex
  • DNA Primers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Interleukin-4
  • Interferon-gamma