Human Innate Mycobacterium tuberculosis– Reactive abTCRþ Thymocytes

PLoS Pathog 4(2):

e39. doi:10.1371/journal.ppat.0040039

Marielle C. Gold1*, Heather D. Ehlinger2, Matthew S. Cook2, Susan K. Smyk-Pearson2, Paul T. Wille3,Ross M. Ungerleider4, Deborah A. Lewinsohn2,3, David M. Lewinsohn1,3
1 Department of Pulmonary and Critical Care Medicine, Portland VA Medical Center, Oregon Health and Science University, Portland, Oregon, United States of America,
2 Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, United States of America, 3 Department of Molecular Microbiology and Immunology,
Oregon Health and Science University, Portland, Oregon, United States of America, 4 Doernbecher Cardiothoracic Surgery, Doernbecher Children’s Hospital, Portland,
Oregon, United States of America.



The control of Mycobacterium tuberculosis (Mtb) infection is heavily dependent on the adaptive Th1 cellular immune response. Paradoxically, optimal priming of the Th1 response requires activation of priming dendritic cells with Th1 cytokine IFN-c. At present, the innate cellular mechanisms required for the generation of an optimal Th1 T cell response remain poorly characterized. We hypothesized that innate Mtb-reactive T cells provide an early source of IFNc to fully activate Mtb-exposed dendritic cells. Here, we report the identification of a novel population of Mtb-reactive CD4 abTCRþ innate thymocytes. These cells are present at high frequencies, respond to Mtb-infected cells by producing IFN-c directly ex vivo, and display characteristics of effector memory T cells. This novel innate population of Mtb-reactive T cells will drive further investigation into the role of these cells in the containment of Mtb following infectious exposure. Furthermore, this is the first demonstration of a human innate pathogen-specific abTCRþ T cell and
is likely to inspire further investigation into innate T cells recognizing other important human pathogens.