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<p>About two billion people are latently infected with <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), which can reside in multiple organs, including the lymphatics. The risk of latent <i>Mtb</i> infection (LTBI) reactivation increases with immunosuppression, such as HIV coinfection, yet the immunological correlates that maintain LTBI remain largely elusive. Using a mouse model of contained lymphatic <i>Mtb</i> infection we dissect the drivers of containment versus reactivation. We show that immunosuppression-induced dissemination of lymphatic <i>Mtb</i> and ensuing progressive disease can be prevented by vaccination with BCG or recombinant BCG even in the absence of CD4<sup>+</sup> T cells. Multi-parameter imaging, spatial transcriptomics and network analysis reveal that anti-CD4-mediated immunosuppression triggers distinct repositioning of non-CD4 immune cells at the edge of TB lesions in cervical lymph nodes. Although B cell numbers increase, they prove dispensable for <i>Mtb</i> containment during CD4<sup>+</sup> T cell loss. Using immune cell-deficient mice, cell depletion and adoptive transfers, we reveal that CD8<sup>+</sup> T cells mediate vaccination-induced prevention of <i>Mtb</i> dissemination in the absence of CD4<sup>+</sup> T cells, informing LTBI management in immunocompromised individuals.</p>

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CD8+ T cells sustain vaccination-induced immunity against dissemination of contained tuberculosis in immunosuppressed hosts

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月24日

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  • Socorro Miranda-Hernandez,
  • Manoharan Kumar,
  • Alec Henderson,
  • Erin Graham,
  • Xiao Tan,
  • Jim Taylor,
  • Michael T. Meehan,
  • Zuriel Ceja,
  • Lidia del Pozo-Ramos,
  • Yi Pan,
  • Ellen Tsui,
  • Meg L. Donovan,
  • Miguel E. Rentería,
  • Mario Alberto Flores-Valdez,
  • Antje Blumenthal,
  • Quan Nguyen,
  • Selvakumar Subbian,
  • Matt A. Field,
  • Andreas Kupz

摘要

About two billion people are latently infected with Mycobacterium tuberculosis (Mtb), which can reside in multiple organs, including the lymphatics. The risk of latent Mtb infection (LTBI) reactivation increases with immunosuppression, such as HIV coinfection, yet the immunological correlates that maintain LTBI remain largely elusive. Using a mouse model of contained lymphatic Mtb infection we dissect the drivers of containment versus reactivation. We show that immunosuppression-induced dissemination of lymphatic Mtb and ensuing progressive disease can be prevented by vaccination with BCG or recombinant BCG even in the absence of CD4+ T cells. Multi-parameter imaging, spatial transcriptomics and network analysis reveal that anti-CD4-mediated immunosuppression triggers distinct repositioning of non-CD4 immune cells at the edge of TB lesions in cervical lymph nodes. Although B cell numbers increase, they prove dispensable for Mtb containment during CD4+ T cell loss. Using immune cell-deficient mice, cell depletion and adoptive transfers, we reveal that CD8+ T cells mediate vaccination-induced prevention of Mtb dissemination in the absence of CD4+ T cells, informing LTBI management in immunocompromised individuals.