Antigen availability shapes T cell differentiation and function during tuberculosis
| Autor: | Albanus O. Moguche, David R. Sherman, Peter Bang, Peter Andersen, Virginie Rozot, Shahin Shafiani, Adam Penn-Nicholson, Thomas J. Scriba, Hennie Geldenhuys, Denise M. McKinney, Deborah Abrahams, Kevin B. Urdahl, Søren T. Hoff, Shuyi Ma, Mark Hatherill, Holden T. Maecker, Willem A. Hanekom, Cecilia S. Lindestam Arlehamn, One B. Dintwe, Munyaradzi Musvosvi, Alessandro Sette, Ingrid Kromann, Courtney R. Plumlee, Helen Mearns, Morten Ruhwald, Ryan P. Larson, Erica Smit |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Antigens Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes Male Lymphocyte Activation Mice South Africa 0302 clinical medicine Tuberculosis Vaccines Lung education.field_of_study biology Vaccination Cell Differentiation respiratory system 3. Good health medicine.anatomical_structure ESAT-6 Cytokines Female Tuberculosis vaccines Tuberculosis Adolescent Population Microbiology Article Mycobacterium tuberculosis 03 medical and health sciences Interferon-gamma Antigen Bacterial Proteins Virology medicine Animals Humans RNA Messenger education Antigens Bacterial biology.organism_classification medicine.disease bacterial infections and mycoses Mice Inbred C57BL 030104 developmental biology Immunology Parasitology Memory T cell Acyltransferases 030215 immunology |
| Popis: | CD4 T cells are critical for protective immunity against Mycobacterium tuberculosis (Mtb), the cause of tuberculosis (TB). Yet, to-date, TB vaccine candidates that boost antigen-specific CD4 T cells have conferred little or no protection. Here we examined CD4 T cell responses to two leading TB vaccine antigens, ESAT-6 and Ag85B, in Mtb infected-mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells. The ability of each T cell population to control Mtb in the lungs of mice was restricted for opposite reasons; Ag85B-specific T cells were limited by reduced antigen expression during persistent infection, whereas ESAT-6-specific T cells became functionally exhausted due to chronic antigenic stimulation. Our findings suggest that different vaccination strategies will be required to optimize protection mediated by T cells recognizing antigens expressed at distinct stages of Mtb infection. |
| Databáze: | OpenAIRE |
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