The precarious balance of immune response to Mycobacterium tuberculosis … are T regulatory cells predictive of infection outcome in a non-human primate model of tuberculosis? (43.5)

Abstract

Abstract A majority of persons infected with M.tb contain but do not eliminate the bacteria, while a minority, develop active tuberculosis. Recent studies in humans suggest an increased frequency of CD4+CD25+ Treg cells in peripheral blood correlates with active TB. To determine whether an increased frequency of CD4+FoxP3+ Treg cells in the periphery is predictive of active disease, we used the non-human primate model of TB, the only animal model that mimics both human latent infection and active disease. Cynomolgus macaques (24) were infected with low dose M.tb and followed until disease state (active or latent) was declared (6–8 months). All animals demonstrated a decrease in the frequency of Tregs following infection until ~ 2 months p.i. without a change in frequency of total CD4+ T cells. Concurrently, the frequency of Tregs and total CD4 T cells in the airways increased up to ~ 2 months p.i. Prior to and 8 weeks p.i., monkeys that eventually presented as latently infected had a significantly higher frequency of Tregs within the CD4 compartment (p< 0.05 and p< 0.005 respectively) than monkeys that eventually had active disease. Between 12–20 weeks, there was a trend toward a higher frequency of Tregs in the monkeys with active disease. Our results suggest frequency of Treg in the periphery may predict or serve as a marker for infection outcome, depending on the stage of infection. NIH grant: RO1 AI50732-01