CD4(+) Regulatory T Cells in a Cynomolgus Macaque Model of Mycobacterium Tuberculosis Infection

J Infect Dis. 2010 Aug 15;202(4):533-41. doi: 10.1086/654896.

Abstract

Background: Mycobacterium tuberculosis infection in humans results in either latent infection or active tuberculosis. We sought to determine whether a higher frequency of regulatory T (T(reg)) cells predispose an individual toward active disease or whether T(reg) cells develop in response to active disease.

Methods: In cynomolgus macaques infected with a low dose of M. tuberculosis, approximately 50% develop primary tuberculosis, and approximately 50% become latently infected. Forty-one animals were monitored for 6-8 months to assess the correlation of the frequency of Foxp3(+) cells in peripheral blood and airways with the outcome of infection.

Results: In all animals, the frequency of T(reg) cells (CD4(+)Foxp3(+)) in peripheral blood rapidly decreased and simultaneously increased in the airways. Latently infected monkeys had a significantly higher frequency of T(reg) cells in peripheral blood before infection and during early infection, compared with monkeys that developed active disease. Monkeys with active disease experienced increased frequencies of T(reg) cells among peripheral blood mononuclear cells as they developed disease.

Conclusions: Our data suggest that increased frequencies of T(reg) cells in active disease occur in response to increased inflammation rather than act as a causative factor in progression to active disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood / immunology
  • CD4 Antigens / analysis
  • Disease Models, Animal
  • Forkhead Transcription Factors / analysis
  • Humans
  • Lung / immunology
  • Lymphocyte Count
  • Macaca
  • Mycobacterium tuberculosis / immunology*
  • T-Lymphocytes, Regulatory / chemistry
  • T-Lymphocytes, Regulatory / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology

Substances

  • CD4 Antigens
  • Forkhead Transcription Factors