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bioRxiv · 10.1101/2022.07.20.500909

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

Moseki, M. R.·Barber, D.·Du Bruyn, E.·Shey, M.·Van der Plas, H.·Wilkinson, R. J.·Meintjes, G.·Riou, C.
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Abstract

BackgroundTuberculosis-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. MethodsWe 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. ResultsIn 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). ConclusionWhile 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.

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Moseki, M. R., Barber, D., Du Bruyn, E., Shey, M., Van der Plas, H., Wilkinson, R. J., Meintjes, G., Riou, C.. 2022-07-22. Phenotypic profile of Mycobacterium tuberculosis-specific CD4 T cell responses in HIV-positive patients who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome. https://doi.org/10.1101/2022.07.20.500909

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