A Subset of Mycobacteria-Specific CD4 IFN-γ T Cell Expressing Naive Phenotype Confers Protection against Tuberculosis Infection in the Lung.

Failure of the most recent tuberculosis (TB) vaccine trial to boost bacillus Calmette-Guérin-mediated anti-TB immunity despite the induction of Th1-specific central memory cell and effector memory cell responses highlights the importance of identifying optimal T cell targets for protective vaccines. In this study， we describe a novel， -specific IFN-γCD4 T cell population expressing surface markers characteristic of naive-like memory T cells (T)， which were induced in both human (CD45RACCR7CD27CD95) and murine (CD62LCD44Sca-1CD122) systems in response to mycobacteria. In bacillus Calmette-Guérin-vaccinated subjects and those with latent TB infection， T were marked by the production of IFN-γ but not TNF-α and identified by the absence of CD95 expression and increased surface expression CCR7， CD27， the activation markers T-bet， CD69， and the survival marker CD74. Increased tetramer-positive T frequencies were noted in the lung and spleen of ESAT-6-specific TCR transgenic mice at 2 wk postinfection with and progressively decreased at later time points， a pattern not seen with TNF-αCD4 T cells expressing naive cell surface markers. Importantly， adoptive transfer of highly purified T alone， from vaccinated ESAT-6-specific TCR transgenic mice， conferred equivalent protection against infection in the lungs of Rag mice when compared with total memory populations (central and effector memory cells). Thus， T may represent a memory T cell population that， if optimally targeted， may significantly improve future TB vaccine responses.