T cell transcription factor expression evolves as adaptive immunity matures in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques

Grant, N. L.; Maiello, P.; Klein, E.; Lin, P. L.; Borish, H. J.; Tomko, J.; Frye, L. J.; White, A. G.; Kirschner, D. E.; Mattila, J. T.; Flynn, J. L.

doi:10.1101/2022.01.25.477732

bioRxiv · 10.1101/2022.01.25.477732

T cell transcription factor expression evolves as adaptive immunity matures in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques

Grant, N. L.·Maiello, P.·Klein, E.·Lin, P. L.·Borish, H. J.·Tomko, J.·Frye, L. J.·White, A. G.·Kirschner, D. E.·Mattila, J. T.·Flynn, J. L.

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Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host control of bacterial replication. We identified and compared the pathological, cellular, and functional differences in granulomas at 4, 12, and 20 weeks post-infection in Chinese cynomolgus macaques. Original granulomas differed in transcription factor expression within adaptive lymphocytes with those at 12 weeks showing higher frequencies of CD8+T-bet+ T cells, while increases in CD4+T-bet+ T cells were observed at 20 weeks post-infection. The appearance of T-bet+ adaptive T cells at 12 and 20 weeks was coincident with a reduction in bacterial burden, suggesting their critical role in Mtb control. This study highlights the evolution of T cell responses within lung granulomas, suggesting that vaccines promoting the development and migration of T-bet+ T cells would enhance mycobacterial control.

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Grant, N. L., Maiello, P., Klein, E., Lin, P. L., Borish, H. J., Tomko, J., Frye, L. J., White, A. G., Kirschner, D. E., Mattila, J. T., Flynn, J. L.. 2022-01-26. T cell transcription factor expression evolves as adaptive immunity matures in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques. https://doi.org/10.1101/2022.01.25.477732

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