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

Miranda-Hernandez, S; Kumar, M; Henderson, A; Graham, E; Tan, X; Taylor, J; Meehan, MT; Ceja, Z; Del Pozo-Ramos, L; Pan, Y; Tsui, E; Donovan, ML; Renter&#237;a, ME; Flores-Valdez, MA; Blumenthal, A; Nguyen, Q; Subbian, S; Field, MA; Kupz, A

Author(s): Miranda-Hernandez, S; Kumar, M; Henderson, A; Graham, E; Tan, X; Taylor, J; Meehan, MT; Ceja, Z; Del Pozo-Ramos, L; Pan, Y; Tsui, E; Donovan, ML; Rentería, ME; Flores-Valdez, MA; Blumenthal, A; Nguyen, Q; Subbian, S; Field, MA; Kupz, A;
Details: Publication Year 2026-03-24,Volume 17,Issue #1,Page 4476
Journal Title: Nature Communications
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.
Publisher: Springer Nature
Keywords: Animals; *CD8-Positive T-Lymphocytes/immunology; *Immunocompromised Host/immunology; *Mycobacterium tuberculosis/immunology; Mice; CD4-Positive T-Lymphocytes/immunology; Vaccination; Mice, Inbred C57BL; *Latent Tuberculosis/immunology/prevention & control/microbiology; BCG Vaccine/immunology; Disease Models, Animal; Lymph Nodes/immunology/microbiology; Female; *Tuberculosis/immunology/prevention & control; Adoptive Transfer; Humans
Research Division(s): Advanced Technology and Biology
PubMed ID: 41876499
Publisher's Version: https://doi.org/10.1038/s41467-026-70911-4
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-026-70911-4
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-05-25 11:04:07

Last Modified: 2026-05-25 11:04:18