CD4+Regulatory T Cells in a Cynomolgus Macaque Model ofMycobacterium tuberculosisInfection

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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 (Treg) cells predispose an individual toward active disease or whether Treg cells develop in response to active disease. Methods. In cynomolgus macaques infected with a low dose of M. tuberculosis, ∼50% develop primary tuberculosis, and ∼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 Treg cells (CD4+Foxp3+) in peripheral blood rapidly decreased and simultaneously increased in the airways. Latently infected monkeys had a significantly higher frequency of Treg 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 Treg cells among peripheral blood mononuclear cells as they developed disease. Conclusions. Our data suggest that increased frequencies of Treg cells in active disease occur in response to increased inflammation rather than act as a causative factor in progression to active disease.