title: Frequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatment.
abstract: 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.
authors: Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors: Rebecca
authors: R
authors: Axelsson-Robertson
authors: Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Hälsovägen F79, Karolinska University Hospital Huddinge Campus, SE14186, Stockholm, Sweden.
authors: Martin
authors: M
authors: Rao
authors: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, South Africa.
authors: Andre G
authors: AG
authors: Loxton
authors: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, South Africa.
authors: Gerhard
authors: G
authors: Walzl
authors: Division of Infection and Immunity, University College London, London, UK; UNZA-UCLMs Research and Training Project, University Teaching Hospital, Lusaka, Zambia.
authors: Matthew
authors: M
authors: Bates
authors: Division of Infection and Immunity, University College London, London, UK; UNZA-UCLMs Research and Training Project, University Teaching Hospital, Lusaka, Zambia; NIHR Biomaedical Research Centre at University College London Hospitals, London, UK.
authors: Alimuddin
authors: A
authors: Zumla
authors: Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden; Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Hälsovägen F79, Karolinska University Hospital Huddinge Campus, SE14186, Stockholm, Sweden. Electronic address: markus.maeurer@ki.se.
authors: Markus
authors: M
authors: Maeurer
mesh_terms: D000328:Adult; D000483:Alleles; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D015395:Histocompatibility Antigens Class I
keywords: CD8+ T-cells; MHC; Multimers; Mycobacterium tuberculosis; Tetramers