@article{Mpande2021,
abstract = {Reversion of immune sensitization tests for Mycobacterium tuberculosis (M.tb) infection, such as interferon-gamma release assays or tuberculin skin test, has been reported in multiple studies. We hypothesised that QuantiFERON-TB Gold (QFT) reversion is associated with a decline of M.tb-specific functional T cell responses, and a distinct pattern of T cell and innate responses compared to persistent QFT+ and QFT- individuals. We compared groups of healthy adolescents (n={\~{}}30 each), defined by four, 6-monthly QFT tests: reverters (QFT+/+/-/-), non-converters (QFT-/-/-/-) and persistent positives (QFT+/+/+/+). We stimulated peripheral blood mononuclear cells with M.tb antigens (M.tb lysate; CFP-10/ESAT-6 and EspC/EspF/Rv2348 peptide pools) and measured M.tb-specific adaptive T cell memory, activation, and functional profiles; as well as functional innate (monocytes, natural killer cells), donor-unrestricted T cells (DURT: $\delta$ T cells, mucosal-associated invariant T and natural killer T-like cells) and B cells by flow cytometry. Projection to latent space discriminant analysis was applied to determine features that best distinguished between QFT reverters, non-converters and persistent positives. No longitudinal changes in immune responses to M.tb were observed upon QFT reversion. M.tb-specific Th1 responses detected in reverters were of intermediate magnitude, higher than responses in QFT non-converters and lower than responses in persistent positives. About one third of reverters had a robust response to CFP-10/ESAT-6. Among those with measurable responses, lower proportions of TSCM (CD45RA+CCR7+CD27+) and early differentiated (CD45RA-) IFN--TNF+IL-2- M.tb lysate-specific CD4+ cells were observed in reverters compared with non-converters. Conversely, higher proportions of early differentiated and lower proportions of effector (CD45RA-CCR7-) CFP10/ESAT6-specific Th1 cells were observed in reverters compared to persistent-positives. No differences in M.tb-specific innate, DURT or B cell functional responses were observed between the groups. Statistical modelling misclassified the majority of reverters as non-converters more frequently than they were correctly classified as reverters or misclassified as persistent positives. These findings suggest that QFT reversion occurs in a heterogeneous group of individuals with low M.tb-specific T cell responses. In some individuals QFT reversion may result from assay variability, while in others the magnitude and differentiation status of M.tb-specific Th1 cells are consistent with well-controlled M.tb infection.},
author = {Mpande, Cheleka A M and Steigler, Pia and Lloyd, Tessa and Rozot, Virginie and Mosito, Boitumelo and Schreuder, Constance and Reid, Timothy D and Bilek, Nicole and Ruhwald, Morten and Andrews, Jason R and Hatherill, Mark and Little, Francesca and Scriba, Thomas J and Nemes, Elisa},
doi = {10.3389/FIMMU.2021.712480},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Mpande et al. - 2021 - Mycobacterium tuberculosis-specific T cell functional, memory, and activation profiles in QuantiFERON-reverters a.pdf:pdf},
issn = {1664-3224},
journal = {Frontiers in Immunology},
keywords = {Mycobacterium tuberculosis infection,OA,QuantiFERON reversion,donor unrestricted T cells,fund{\_}ack,innate immune response,memory T cell,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {aug},
pages = {712480},
pmid = {34526988},
publisher = {Frontiers},
title = {{Mycobacterium tuberculosis-specific T cell functional, memory, and activation profiles in QuantiFERON-reverters are consistent with controlled infection}},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.712480/full},
volume = {12},
year = {2021}
}

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We compared groups of healthy adolescents (n=\\ 30 each), defined by four, 6-monthly QFT tests: reverters (QFT+/+/-/-), non-converters (QFT-/-/-/-) and persistent positives (QFT+/+/+/+). We stimulated peripheral blood mononuclear cells with M.tb antigens (M.tb lysate; CFP-10/ESAT-6 and EspC/EspF/Rv2348 peptide pools) and measured M.tb-specific adaptive T cell memory, activation, and functional profiles; as well as functional innate (monocytes, natural killer cells), donor-unrestricted T cells (DURT: $δ$ T cells, mucosal-associated invariant T and natural killer T-like cells) and B cells by flow cytometry. Projection to latent space discriminant analysis was applied to determine features that best distinguished between QFT reverters, non-converters and persistent positives. No longitudinal changes in immune responses to M.tb were observed upon QFT reversion. M.tb-specific Th1 responses detected in reverters were of intermediate magnitude, higher than responses in QFT non-converters and lower than responses in persistent positives. About one third of reverters had a robust response to CFP-10/ESAT-6. Among those with measurable responses, lower proportions of TSCM (CD45RA+CCR7+CD27+) and early differentiated (CD45RA-) IFN--TNF+IL-2- M.tb lysate-specific CD4+ cells were observed in reverters compared with non-converters. Conversely, higher proportions of early differentiated and lower proportions of effector (CD45RA-CCR7-) CFP10/ESAT6-specific Th1 cells were observed in reverters compared to persistent-positives. No differences in M.tb-specific innate, DURT or B cell functional responses were observed between the groups. Statistical modelling misclassified the majority of reverters as non-converters more frequently than they were correctly classified as reverters or misclassified as persistent positives. These findings suggest that QFT reversion occurs in a heterogeneous group of individuals with low M.tb-specific T cell responses. In some individuals QFT reversion may result from assay variability, while in others the magnitude and differentiation status of M.tb-specific Th1 cells are consistent with well-controlled M.tb infection.","author":[{"propositions":[],"lastnames":["Mpande"],"firstnames":["Cheleka","A","M"],"suffixes":[]},{"propositions":[],"lastnames":["Steigler"],"firstnames":["Pia"],"suffixes":[]},{"propositions":[],"lastnames":["Lloyd"],"firstnames":["Tessa"],"suffixes":[]},{"propositions":[],"lastnames":["Rozot"],"firstnames":["Virginie"],"suffixes":[]},{"propositions":[],"lastnames":["Mosito"],"firstnames":["Boitumelo"],"suffixes":[]},{"propositions":[],"lastnames":["Schreuder"],"firstnames":["Constance"],"suffixes":[]},{"propositions":[],"lastnames":["Reid"],"firstnames":["Timothy","D"],"suffixes":[]},{"propositions":[],"lastnames":["Bilek"],"firstnames":["Nicole"],"suffixes":[]},{"propositions":[],"lastnames":["Ruhwald"],"firstnames":["Morten"],"suffixes":[]},{"propositions":[],"lastnames":["Andrews"],"firstnames":["Jason","R"],"suffixes":[]},{"propositions":[],"lastnames":["Hatherill"],"firstnames":["Mark"],"suffixes":[]},{"propositions":[],"lastnames":["Little"],"firstnames":["Francesca"],"suffixes":[]},{"propositions":[],"lastnames":["Scriba"],"firstnames":["Thomas","J"],"suffixes":[]},{"propositions":[],"lastnames":["Nemes"],"firstnames":["Elisa"],"suffixes":[]}],"doi":"10.3389/FIMMU.2021.712480","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Mpande et al. - 2021 - Mycobacterium tuberculosis-specific T cell functional, memory, and activation profiles in QuantiFERON-reverters a.pdf:pdf","issn":"1664-3224","journal":"Frontiers in Immunology","keywords":"Mycobacterium tuberculosis infection,OA,QuantiFERON reversion,donor unrestricted T cells,fund_ack,innate immune response,memory T cell,original","mendeley-tags":"OA,fund_ack,original","month":"aug","pages":"712480","pmid":"34526988","publisher":"Frontiers","title":"Mycobacterium tuberculosis-specific T cell functional, memory, and activation profiles in QuantiFERON-reverters are consistent with controlled infection","url":"https://www.frontiersin.org/articles/10.3389/fimmu.2021.712480/full","volume":"12","year":"2021","bibtex":"@article{Mpande2021,\r\nabstract = {Reversion of immune sensitization tests for Mycobacterium tuberculosis (M.tb) infection, such as interferon-gamma release assays or tuberculin skin test, has been reported in multiple studies. We hypothesised that QuantiFERON-TB Gold (QFT) reversion is associated with a decline of M.tb-specific functional T cell responses, and a distinct pattern of T cell and innate responses compared to persistent QFT+ and QFT- individuals. We compared groups of healthy adolescents (n={\\~{}}30 each), defined by four, 6-monthly QFT tests: reverters (QFT+/+/-/-), non-converters (QFT-/-/-/-) and persistent positives (QFT+/+/+/+). We stimulated peripheral blood mononuclear cells with M.tb antigens (M.tb lysate; CFP-10/ESAT-6 and EspC/EspF/Rv2348 peptide pools) and measured M.tb-specific adaptive T cell memory, activation, and functional profiles; as well as functional innate (monocytes, natural killer cells), donor-unrestricted T cells (DURT: $\\delta$ T cells, mucosal-associated invariant T and natural killer T-like cells) and B cells by flow cytometry. Projection to latent space discriminant analysis was applied to determine features that best distinguished between QFT reverters, non-converters and persistent positives. No longitudinal changes in immune responses to M.tb were observed upon QFT reversion. M.tb-specific Th1 responses detected in reverters were of intermediate magnitude, higher than responses in QFT non-converters and lower than responses in persistent positives. About one third of reverters had a robust response to CFP-10/ESAT-6. Among those with measurable responses, lower proportions of TSCM (CD45RA+CCR7+CD27+) and early differentiated (CD45RA-) IFN--TNF+IL-2- M.tb lysate-specific CD4+ cells were observed in reverters compared with non-converters. Conversely, higher proportions of early differentiated and lower proportions of effector (CD45RA-CCR7-) CFP10/ESAT6-specific Th1 cells were observed in reverters compared to persistent-positives. No differences in M.tb-specific innate, DURT or B cell functional responses were observed between the groups. Statistical modelling misclassified the majority of reverters as non-converters more frequently than they were correctly classified as reverters or misclassified as persistent positives. These findings suggest that QFT reversion occurs in a heterogeneous group of individuals with low M.tb-specific T cell responses. In some individuals QFT reversion may result from assay variability, while in others the magnitude and differentiation status of M.tb-specific Th1 cells are consistent with well-controlled M.tb infection.},\r\nauthor = {Mpande, Cheleka A M and Steigler, Pia and Lloyd, Tessa and Rozot, Virginie and Mosito, Boitumelo and Schreuder, Constance and Reid, Timothy D and Bilek, Nicole and Ruhwald, Morten and Andrews, Jason R and Hatherill, Mark and Little, Francesca and Scriba, Thomas J and Nemes, Elisa},\r\ndoi = {10.3389/FIMMU.2021.712480},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Mpande et al. - 2021 - Mycobacterium tuberculosis-specific T cell functional, memory, and activation profiles in QuantiFERON-reverters a.pdf:pdf},\r\nissn = {1664-3224},\r\njournal = {Frontiers in Immunology},\r\nkeywords = {Mycobacterium tuberculosis infection,OA,QuantiFERON reversion,donor unrestricted T cells,fund{\\_}ack,innate immune response,memory T cell,original},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {aug},\r\npages = {712480},\r\npmid = {34526988},\r\npublisher = {Frontiers},\r\ntitle = {{Mycobacterium tuberculosis-specific T cell functional, memory, and activation profiles in QuantiFERON-reverters are consistent with controlled infection}},\r\nurl = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.712480/full},\r\nvolume = {12},\r\nyear = {2021}\r\n}\r\n","author_short":["Mpande, C. 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