Phenotypic profile of Mycobacterium tuberculosis-specific CD4 T cell responses in people with advanced HIV who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome

Phenotypic profile of Mycobacterium tuberculosis-specific CD4 T cell responses in people with advanced HIV who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome. Moseki, R. M, Barber, D. L, Du Bruyn, E., Shey, M., Van der Plas, H., Wilkinson, R. J, Meintjes, G., & Riou, C. Open Forum Infectious Diseases, 10(1):ofac546, oct, 2023.

Paper doi abstract bibtex

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of cotreatment for TB and human immunodeficiency virus (HIV)-1. We characterized Mycobacterium tuberculosis (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 used a longitudinal study design to compare the magnitude of antiretroviral therapy, 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 Eomesodermin (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 = .039). Patients with TB-IRIS had higher HLA-DR expression (P = .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 patients with TB-IRIS (P = .026). Conclusions Although the murine model of Mycobacterium avium complex-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mycobacterium tuberculosis-specific IFN$γ$+CD4 T-cell responses in TB-IRIS patients are differentiated, highly activated, and potentially cytotoxic.

@article{Moseki2022a,
abstract = {Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of cotreatment for TB and human immunodeficiency virus (HIV)-1. We characterized Mycobacterium tuberculosis (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 used a longitudinal study design to compare the magnitude of antiretroviral therapy, 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 Eomesodermin (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 = .039). Patients with TB-IRIS had higher HLA-DR expression (P = .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 patients with TB-IRIS (P = .026). Conclusions Although the murine model of Mycobacterium avium complex-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mycobacterium tuberculosis-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 {Du Bruyn}, Elsa and Shey, Muki and {Van der Plas}, Helen and Wilkinson, Robert J and Meintjes, Graeme and Riou, Catherine},
doi = {10.1093/OFID/OFAC546},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moseki et al. - 2023 - Phenotypic profile of Mycobacterium tuberculosis-specific CD4 T cell responses in people with advanced HIV who de.pdf:pdf},
issn = {2328-8957},
journal = {Open Forum Infectious Diseases},
keywords = {HIV-1/TB coinfection,OA,OA{\_}PMC,Th1 responses,fund{\_}ack,immune activation,original,paradoxical TB-IRIS},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,original},
month = {oct},
number = {1},
pages = {ofac546},
pmid = {36726536},
title = {{Phenotypic profile of \textit{Mycobacterium tuberculosis}-specific CD4 T cell responses in people with advanced HIV who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome}},
url = {https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac546/6761821},
volume = {10},
year = {2023}
}

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In humans, we used a longitudinal study design to compare the magnitude of antiretroviral therapy, 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 Eomesodermin (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 = .039). Patients with TB-IRIS had higher HLA-DR expression (P = .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 patients with TB-IRIS (P = .026). Conclusions Although the murine model of Mycobacterium avium complex-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. 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