CD4(+) regulatory T cells in a cynomolgus macaque model of Mycobacterium tuberculosis infection.
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.
Green
Angela M
AM
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Mattila
Joshua T
JT
Bigbee
Carolyn L
CL
Bongers
Kale S
KS
Lin
P Ling
PL
Flynn
Joanne L
JL
D000818:Animals; D001769:Blood / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D008168:Lung / Q000276:immunology; D018655:Lymphocyte Count; D008251:Macaca; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors