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, similar to 50% develop primary tuberculosis, and similar to 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.