Mycobacterium tuberculosis-Specific Cellular Immune Profiles Suggest Bacillary Persistence Decades after Spontaneous Cure in Untreated Tuberculosis

Individuals with self-healed tuberculosis from the preantibiotic era offer a unique insight into the natural history of and protective immunity to tuberculosis. In 27 such persons whose tuberculosis self-healed 150 years earlier, circulating Mycobacterium tuberculosis antigen-specific interferon gamma (IFN-gamma)- and interleukin 2 (IL-2)-secreting T cells were detected ex vivo in 16 and 19 individuals, respectively. The M. tuberculosis-specific T cell cytokine profile was dominated by effector memory T cells that secrete both IFN-gamma and IL-2 and included T cells that secrete only IFN-gamma or IL-2, suggesting persistence of antigen secreted by viable bacilli. Of 10 individuals with no M. tuberculosis antigen-specific IFN-gamma-secreting T cells detectable ex vivo, 7 had evidence of central memory T cells, consistent with clearance of infection.