@article{Moseki2022,
abstract = {Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of co-treatment for TB and HIV-1. We characterized Mtb-specific CD4 T cell phenotype and transcription factor profile associated with the development of TB-IRIS. Methods We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we compared longitudinally on antiretroviral therapy (ART) the magnitude, activation, transcription factor profile and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n=25) and appropriate non-IRIS control patients (n=18) using flow cytometry. Results In the murine model, CD4 T cell expression of Eomes, but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFN$\gamma$+CD4 T cells (p=0.039). TB-IRIS patients had higher HLA-DR expression (p=0.016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+Tbet+Mtb-specific IFN$\gamma$+CD4+ T cells showed higher expression of Granzyme B in TB-IRIS patients (p=0.026). Conclusion While the murine model of MAC-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mtb-specific IFN$\gamma$+CD4 T cell responses in TB-IRIS patients are differentiated, highly activated and potentially cytotoxic.},
author = {Moseki, Raymond M and Barber, Daniel L and Bruyn, Elsa Du and Shey, Muki and der Plas, Helen Van and Wilkinson, Robert J and Meintjes, Graeme and Riou, Catherine},
doi = {10.1101/2022.07.20.500909},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moseki et al. - 2022 - Phenotypic profile of iMycobacterium tuberculosisi-specific CD4 T cell responses in HIV-positive patients who dev.pdf:pdf},
journal = {bioRxiv},
keywords = {HIV-1/TB coinfection,OA,Th1 responses,fund{\_}ack,immune activation,original,paradoxical TB-IRIS},
mendeley-tags = {OA,fund{\_}ack,original},
month = {jul},
pages = {2022.07.20.500909},
publisher = {Cold Spring Harbor Laboratory},
title = {{Phenotypic profile of \textit{Mycobacterium tuberculosis}-specific CD4 T cell responses in HIV-positive patients who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome}},
url = {https://www.biorxiv.org/content/10.1101/2022.07.20.500909v1 https://www.biorxiv.org/content/10.1101/2022.07.20.500909v1.abstract},
year = {2022}
}

{"_id":"ga3gavwsS7uWiyjnR","bibbaseid":"moseki-barber-bruyn-shey-derplas-wilkinson-meintjes-riou-phenotypicprofileofimycobacteriumtuberculosisispecificcd4tcellresponsesinhivpositivepatientswhodeveloptuberculosisassociatedimmunereconstitutioninflammatorysyndrome-2022","author_short":["Moseki, R. M","Barber, D. L","Bruyn, E. D.","Shey, M.","der Plas, H. V.","Wilkinson, R. J","Meintjes, G.","Riou, C."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of co-treatment for TB and HIV-1. We characterized Mtb-specific CD4 T cell phenotype and transcription factor profile associated with the development of TB-IRIS. Methods We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we compared longitudinally on antiretroviral therapy (ART) the magnitude, activation, transcription factor profile and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n=25) and appropriate non-IRIS control patients (n=18) using flow cytometry. Results In the murine model, CD4 T cell expression of Eomes, but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFN$γ$+CD4 T cells (p=0.039). TB-IRIS patients had higher HLA-DR expression (p=0.016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+Tbet+Mtb-specific IFN$γ$+CD4+ T cells showed higher expression of Granzyme B in TB-IRIS patients (p=0.026). Conclusion While the murine model of MAC-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mtb-specific IFN$γ$+CD4 T cell responses in TB-IRIS patients are differentiated, highly activated and potentially cytotoxic.","author":[{"propositions":[],"lastnames":["Moseki"],"firstnames":["Raymond","M"],"suffixes":[]},{"propositions":[],"lastnames":["Barber"],"firstnames":["Daniel","L"],"suffixes":[]},{"propositions":[],"lastnames":["Bruyn"],"firstnames":["Elsa","Du"],"suffixes":[]},{"propositions":[],"lastnames":["Shey"],"firstnames":["Muki"],"suffixes":[]},{"propositions":["der"],"lastnames":["Plas"],"firstnames":["Helen","Van"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme"],"suffixes":[]},{"propositions":[],"lastnames":["Riou"],"firstnames":["Catherine"],"suffixes":[]}],"doi":"10.1101/2022.07.20.500909","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moseki et al. - 2022 - Phenotypic profile of iMycobacterium tuberculosisi-specific CD4 T cell responses in HIV-positive patients who dev.pdf:pdf","journal":"bioRxiv","keywords":"HIV-1/TB coinfection,OA,Th1 responses,fund_ack,immune activation,original,paradoxical TB-IRIS","mendeley-tags":"OA,fund_ack,original","month":"jul","pages":"2022.07.20.500909","publisher":"Cold Spring Harbor Laboratory","title":"Phenotypic profile of <i>Mycobacterium tuberculosis</i>-specific CD4 T cell responses in HIV-positive patients who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome","url":"https://www.biorxiv.org/content/10.1101/2022.07.20.500909v1 https://www.biorxiv.org/content/10.1101/2022.07.20.500909v1.abstract","year":"2022","bibtex":"@article{Moseki2022,\r\nabstract = {Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of co-treatment for TB and HIV-1. We characterized Mtb-specific CD4 T cell phenotype and transcription factor profile associated with the development of TB-IRIS. Methods We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we compared longitudinally on antiretroviral therapy (ART) the magnitude, activation, transcription factor profile and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n=25) and appropriate non-IRIS control patients (n=18) using flow cytometry. Results In the murine model, CD4 T cell expression of Eomes, but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFN$\\gamma$+CD4 T cells (p=0.039). TB-IRIS patients had higher HLA-DR expression (p=0.016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+Tbet+Mtb-specific IFN$\\gamma$+CD4+ T cells showed higher expression of Granzyme B in TB-IRIS patients (p=0.026). Conclusion While the murine model of MAC-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mtb-specific IFN$\\gamma$+CD4 T cell responses in TB-IRIS patients are differentiated, highly activated and potentially cytotoxic.},\r\nauthor = {Moseki, Raymond M and Barber, Daniel L and Bruyn, Elsa Du and Shey, Muki and der Plas, Helen Van and Wilkinson, Robert J and Meintjes, Graeme and Riou, Catherine},\r\ndoi = {10.1101/2022.07.20.500909},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moseki et al. - 2022 - Phenotypic profile of iMycobacterium tuberculosisi-specific CD4 T cell responses in HIV-positive patients who dev.pdf:pdf},\r\njournal = {bioRxiv},\r\nkeywords = {HIV-1/TB coinfection,OA,Th1 responses,fund{\\_}ack,immune activation,original,paradoxical TB-IRIS},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {jul},\r\npages = {2022.07.20.500909},\r\npublisher = {Cold Spring Harbor Laboratory},\r\ntitle = {{Phenotypic profile of \\textit{Mycobacterium tuberculosis}-specific CD4 T cell responses in HIV-positive patients who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome}},\r\nurl = {https://www.biorxiv.org/content/10.1101/2022.07.20.500909v1 https://www.biorxiv.org/content/10.1101/2022.07.20.500909v1.abstract},\r\nyear = {2022}\r\n}\r\n","author_short":["Moseki, R. 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