Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy
Background: The analysis of phenotypic characteristics on Mycobacterium tuberculosis (MTB)-specific T cells is a promising approach for the diagnosis of active tuberculosis (aTB) and for monitoring treatment success. We therefore studied phenotypic changes on MTB-specific CD4 T cells upon anti-tuber...
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02247/full |
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| author | Mohamed I. M. Ahmed Mohamed I. M. Ahmed Mohamed I. M. Ahmed Nyanda E. Ntinginya Gibson Kibiki Bariki A Mtafya Hadija Semvua Stellah Mpagama Charles Mtabho Elmar Saathoff Elmar Saathoff Kathrin Held Kathrin Held Rebecca Loose Rebecca Loose Inge Kroidl Inge Kroidl Mkunde Chachage Mkunde Chachage Ulrich von Both Ulrich von Both Ulrich von Both Antelmo Haule Anna-Maria Mekota Anna-Maria Mekota Martin J. Boeree Stephen H. Gillespie Michael Hoelscher Michael Hoelscher Norbert Heinrich Norbert Heinrich Christof Geldmacher Christof Geldmacher |
| author_facet | Mohamed I. M. Ahmed Mohamed I. M. Ahmed Mohamed I. M. Ahmed Nyanda E. Ntinginya Gibson Kibiki Bariki A Mtafya Hadija Semvua Stellah Mpagama Charles Mtabho Elmar Saathoff Elmar Saathoff Kathrin Held Kathrin Held Rebecca Loose Rebecca Loose Inge Kroidl Inge Kroidl Mkunde Chachage Mkunde Chachage Ulrich von Both Ulrich von Both Ulrich von Both Antelmo Haule Anna-Maria Mekota Anna-Maria Mekota Martin J. Boeree Stephen H. Gillespie Michael Hoelscher Michael Hoelscher Norbert Heinrich Norbert Heinrich Christof Geldmacher Christof Geldmacher |
| author_sort | Mohamed I. M. Ahmed |
| collection | DOAJ |
| description | Background: The analysis of phenotypic characteristics on Mycobacterium tuberculosis (MTB)-specific T cells is a promising approach for the diagnosis of active tuberculosis (aTB) and for monitoring treatment success. We therefore studied phenotypic changes on MTB-specific CD4 T cells upon anti-tuberculosis treatment initiation in relation to the treatment response as determined by sputum culture.Methods: Peripheral blood mononuclear cells from subjects with latent MTB infection (n = 16) and aTB (n = 39) at baseline, weeks 9, 12, and 26 (end of treatment) were analyzed after intracellular interferon gamma staining and overnight stimulation with tuberculin. Liquid sputum cultures were performed weekly until week 12 and during 4 visits until week 26.Results: T cell activation marker expression on MTB-specific CD4 T cells differed significantly between subjects with aTB and latent MTB infection with no overlap for the frequencies of CD38pos and Ki67pos cells (both p < 0.0001). At 9 weeks after anti-TB treatment initiation the frequencies of activation marker (CD38, HLA-DR, Ki67) positive MTB-specific, but not total CD4 T cells, were significantly reduced (p < 0.0001). Treatment induced phenotypic changes from baseline until week 9 and until week 12 differed substantially between individual aTB patients and correlated with an individual's time to stable sputum culture conversion for expression of CD38 and HLA-DR (both p < 0.05). In contrast, the frequencies of maturation marker CD27 positive MTB-specific CD4 T cells remained largely unchanged until week 26 and significantly differed between subjects with treated TB disease and latent MTB infection (p = 0.0003).Discussion: Phenotypic changes of MTB-specific T cells are potential surrogate markers for tuberculosis treatment efficacy and can help to discriminate between aTB (profile: CD38pos, CD27low), treated TB (CD38neg, CD27low), and latent MTB infection (CD38neg, CD27high). |
| first_indexed | 2024-12-24T13:07:39Z |
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| id | doaj.art-59cf6a1fcb3c47898c491699e3ae9790 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T13:07:39Z |
| publishDate | 2018-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-59cf6a1fcb3c47898c491699e3ae97902022-12-21T16:53:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-09-01910.3389/fimmu.2018.02247386378Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment EfficacyMohamed I. M. Ahmed0Mohamed I. M. Ahmed1Mohamed I. M. Ahmed2Nyanda E. Ntinginya3Gibson Kibiki4Bariki A Mtafya5Hadija Semvua6Stellah Mpagama7Charles Mtabho8Elmar Saathoff9Elmar Saathoff10Kathrin Held11Kathrin Held12Rebecca Loose13Rebecca Loose14Inge Kroidl15Inge Kroidl16Mkunde Chachage17Mkunde Chachage18Ulrich von Both19Ulrich von Both20Ulrich von Both21Antelmo Haule22Anna-Maria Mekota23Anna-Maria Mekota24Martin J. Boeree25Stephen H. Gillespie26Michael Hoelscher27Michael Hoelscher28Norbert Heinrich29Norbert Heinrich30Christof Geldmacher31Christof Geldmacher32Division of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyCIH LMU Center for International Health, Klinikum of the University of Munich, Munich, GermanyNational Institute for Medical Research—Mbeya Medical Research Center, Mbeya, TanzaniaKilimanjaro Christian Medical Centre, Kilimanjaro Clinical Research Institute, Moshi, TanzaniaNational Institute for Medical Research—Mbeya Medical Research Center, Mbeya, TanzaniaKilimanjaro Christian Medical Centre, Kilimanjaro Clinical Research Institute, Moshi, TanzaniaKilimanjaro Christian Medical Centre, Kilimanjaro Clinical Research Institute, Moshi, TanzaniaKilimanjaro Christian Medical Centre, Kilimanjaro Clinical Research Institute, Moshi, TanzaniaDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyNational Institute for Medical Research—Mbeya Medical Research Center, Mbeya, TanzaniaDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyDr. von Hauner Children's Hospital, Division of Paediatric Infectious Diseases, Klinikum of the University of Munich (LMU), Munich, GermanyNational Institute for Medical Research—Mbeya Medical Research Center, Mbeya, TanzaniaDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyDepartment of Lung Diseases, Radboud University Medical Centre Nijmegen, Nijmegen, NetherlandsInfection and Global Health Research Division, University of St Andrews, St Andrews, United KingdomDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyDivision of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich (LMU), Munich, GermanyGerman Center for Infection Research (DZIF), Partner Site Munich, Munich, GermanyBackground: The analysis of phenotypic characteristics on Mycobacterium tuberculosis (MTB)-specific T cells is a promising approach for the diagnosis of active tuberculosis (aTB) and for monitoring treatment success. We therefore studied phenotypic changes on MTB-specific CD4 T cells upon anti-tuberculosis treatment initiation in relation to the treatment response as determined by sputum culture.Methods: Peripheral blood mononuclear cells from subjects with latent MTB infection (n = 16) and aTB (n = 39) at baseline, weeks 9, 12, and 26 (end of treatment) were analyzed after intracellular interferon gamma staining and overnight stimulation with tuberculin. Liquid sputum cultures were performed weekly until week 12 and during 4 visits until week 26.Results: T cell activation marker expression on MTB-specific CD4 T cells differed significantly between subjects with aTB and latent MTB infection with no overlap for the frequencies of CD38pos and Ki67pos cells (both p < 0.0001). At 9 weeks after anti-TB treatment initiation the frequencies of activation marker (CD38, HLA-DR, Ki67) positive MTB-specific, but not total CD4 T cells, were significantly reduced (p < 0.0001). Treatment induced phenotypic changes from baseline until week 9 and until week 12 differed substantially between individual aTB patients and correlated with an individual's time to stable sputum culture conversion for expression of CD38 and HLA-DR (both p < 0.05). In contrast, the frequencies of maturation marker CD27 positive MTB-specific CD4 T cells remained largely unchanged until week 26 and significantly differed between subjects with treated TB disease and latent MTB infection (p = 0.0003).Discussion: Phenotypic changes of MTB-specific T cells are potential surrogate markers for tuberculosis treatment efficacy and can help to discriminate between aTB (profile: CD38pos, CD27low), treated TB (CD38neg, CD27low), and latent MTB infection (CD38neg, CD27high).https://www.frontiersin.org/article/10.3389/fimmu.2018.02247/fullTAM-TB assaytuberculosistreatment monitoringMycobacterium tuberculosis-specific T cellsserial sputum culturebiomarker |
| spellingShingle | Mohamed I. M. Ahmed Mohamed I. M. Ahmed Mohamed I. M. Ahmed Nyanda E. Ntinginya Gibson Kibiki Bariki A Mtafya Hadija Semvua Stellah Mpagama Charles Mtabho Elmar Saathoff Elmar Saathoff Kathrin Held Kathrin Held Rebecca Loose Rebecca Loose Inge Kroidl Inge Kroidl Mkunde Chachage Mkunde Chachage Ulrich von Both Ulrich von Both Ulrich von Both Antelmo Haule Anna-Maria Mekota Anna-Maria Mekota Martin J. Boeree Stephen H. Gillespie Michael Hoelscher Michael Hoelscher Norbert Heinrich Norbert Heinrich Christof Geldmacher Christof Geldmacher Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy Frontiers in Immunology TAM-TB assay tuberculosis treatment monitoring Mycobacterium tuberculosis-specific T cells serial sputum culture biomarker |
| title | Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy |
| title_full | Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy |
| title_fullStr | Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy |
| title_full_unstemmed | Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy |
| title_short | Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy |
| title_sort | phenotypic changes on mycobacterium tuberculosis specific cd4 t cells as surrogate markers for tuberculosis treatment efficacy |
| topic | TAM-TB assay tuberculosis treatment monitoring Mycobacterium tuberculosis-specific T cells serial sputum culture biomarker |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02247/full |
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