Frequency of Mycobacterium tuberculosis-specific CD8+T-cells in the course of anti-tuberculosis treatment

Axelsson-Robertson, Rebecca, Rao, Martin, Loxton, Andre G. , Walzl, Gerhard, Bates, Matthew, Zumla, Alimuddin and Maeurer, Markus (2015) Frequency of Mycobacterium tuberculosis-specific CD8+T-cells in the course of anti-tuberculosis treatment. International Journal of Infectious Diseases, 32 (SI). pp. 23-29. ISSN 1201-9712

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Anti-tuberculosis drug treatment is known to affect the number, phenotype, and effector functionality of antigen-specific T-cells. In order to objectively gauge Mycobacterium tuberculosis (MTB)-specific CD8+ T-cells at the single-cell level, we developed soluble major histocompatibility complex (MHC) class I multimers/peptide multimers, which allow analysis of antigen-specific T-cells without ex vivo manipulation or functional tests. We constructed 38 MHC class I multimers covering some of the most frequent MHC class I alleles (HLA-A*02:01, A*24:02, A*30:01, A*30:02, A*68:01, B*58:01, and C*07:01) pertinent to a South African or Zambian population, and presenting the following MTB-derived peptides: the early expressed secreted antigens TB10.4 (Rv0288), Ag85B (Rv1886c), and ESAT-6 (Rv3875), as well as intracellular enzymes, i.e., glycosyltransferase 1 (Rv2957), glycosyltransferase 2 (Rv2958c), and cyclopropane fatty acid synthase (Rv0447c). Anti-TB treatment appeared to impact on the frequency of multimer-positive CD8+ T-cells, with a general decrease after 6 months of therapy. Also, a reduction in the total central memory CD8+ T-cell frequencies, as well as the antigen-specific compartment in CD45RA - CCR7+ T-cells was observed. We discuss our findings on the basis of differential dynamics of MTB-specific T-cell frequencies, impact of MTB antigen load on T-cell phenotype, and antigen-specific T-cell responses in tuberculosis. (c) 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Keywords:CD8+T-cell, Mycobacterium tuberculosis, Tetramers, Multimers, MHC}
Subjects:A Medicine and Dentistry > A300 Clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:28367
Deposited On:05 Oct 2017 08:25

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