Miranda-Hernandez, Socorro, Kumar, Manoharan, Henderson, Alec, Graham, Erin, Tan, Xiao, Taylor, Jim, Meehan, Michael, Ceja, Zuriel, Del Pozo Ramos, Lidia Maria, Pan, Yi, Tsui, Ellen, Donovan, Meg L., Rentería, Miguel E., Flores-Valdez, Mario Alberto, Blumenthal, Antje, Nguyen, Quan, Subbian, Selvakumar, Field, Matt, and Kupz, Andreas (2026) CD8+ T cells sustain vaccination-induced immunity against dissemination of contained tuberculosis in immunosuppressed hosts. Nature Communications, 17. 4476.

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Abstract

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.

Item ID:	91301
Item Type:	Article (Research - C1)
ISSN:	2041-1723
Copyright Information:	© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Date Deposited:	26 May 2026 04:37
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320405 Humoural immunology and immunochemistry @ 50%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100%
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