Meng Sun, Jolie M. Phan, Nathan S. Kieswetter, Huang Huang, Krystle K. Q. Yu, Malisa T. Smith, Yiran E. Liu, Chuanqi Wang, Sanjana Gupta, Gerlinde Obermoser, Holden Terry Maecker, Akshaya Krishnan, Sundari Suresh, Neha Gupta, Mary Rieck, Peter Acs, Mustafa Ghanizada, Shin-Heng Chiou, Purvesh Khatri, W. Henry Boom, Thomas R. Hawn, Catherine M. Stein, Harriet Mayanja-Kizza, Mark M. Davis, Chetan Seshadri
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引用次数: 0
Abstract
A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) that we refer to as ‘resisters’ (RSTR) show evidence of IFN-γ− T cell responses to Mtb-specific antigens despite serially negative results on clinical testing. Here we found that Mtb-specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4+ T cells showed enrichment of TH17 and regulatory T cell-like functional programs compared to Mtb-specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these TH17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype. Seshadri, Davis and colleagues show that individuals who do not develop an infection with Mycobacterium tuberculosis (Mtb), despite exposure to the bacteria and expansion of CD4+ T cell clones specific to Mtb antigens, show enrichment of TH17 cell and T regulatory functional programs.
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.