Human Innate Mycobacterium tuberculosis–Reactive αβTCR+ Thymocytes

PLoS Pathogens

David M Lewinsohn¹  Paul T Wille¹  Deborah A Lewinsohn²  Matthew S Cook²  Heather D Ehlinger²  Susan K Smyk-Pearson²  Marielle C Gold³  Ross M Ungerleider⁴ 

[1] Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, United States of America;Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, United States of America;Department of Pulmonary and Critical Care Medicine, Portland VA Medical Center, Oregon Health and Science University, Portland, Oregon, United States of America;Doernbecher Cardiothoracic Surgery, Doernbecher Children's Hospital, Portland, Oregon, United States of America

关键词: Thymocytes;    T cells;    Mycobacterium tuberculosis;    Enzyme-linked immunoassays;    Cytotoxic T cells;    Thymus;    Immune response;    Major histocompatibility complex;   

DOI  :  10.1371/journal.ppat.0040039

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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-γ. 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 IFN-γ to fully activate Mtb-exposed dendritic cells. Here, we report the identification of a novel population of Mtb-reactive CD4− αβTCR+ innate thymocytes. These cells are present at high frequencies, respond to Mtb-infected cells by producing IFN-γ 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 αβTCR+ T cell and is likely to inspire further investigation into innate T cells recognizing other important human pathogens.

【 授权许可】

CC BY