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CD8+ T cells sustain vaccination-induced immunity against dissemination of contained tuberculosis in immunosuppressed hosts
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CD8+ T cells sustain vaccination-induced immunity against dissemination of contained tuberculosis in immunosuppressed hosts
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Journal Article
CD8+ T cells sustain vaccination-induced immunity against dissemination of contained tuberculosis in immunosuppressed hosts
2026
Overview
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.
The immunological events that correlate with latent
Mycobacterium tuberculosis
(
Mtb
) infection (LTBI) containment in immune suppressed hosts remain to be explored. The authors here show that CD8
+
T cells are critical for BCG vaccination-induced prevention of Mtb dissemination in the absence of CD4
+
T cells in a mouse model of contained tuberculosis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 14/63
/ 45/91
/ 631/326
/ 64/60
/ 82/51
/ Animals
/ Bacillus Calmette-Guerin vaccine
/ BCG
/ CD4-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Disease
/ Female
/ HIV
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Humans
/ Immunocompromised Host - immunology
/ Latent Tuberculosis - immunology
/ Latent Tuberculosis - microbiology
/ Latent Tuberculosis - prevention & control
/ Lungs
/ Mice
/ Mycobacterium tuberculosis - immunology
/ Science
/ Tuberculosis - prevention & control
/ Vaccines
