Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes.

Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes.

Publication date: Apr 07, 2025

Tuberculosis (TB) is a major health burden worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the BCG route and dose from 5 cD7 105 CFUs ID to 5 cD7 107 CFUs i. v. resulted in prevention of Mycobacterium tuberculosis (Mtb) infection and TB disease in highly susceptible nonhuman primates. Identifying immune mechanisms protection following i. v. BCG will facilitate development of more effective vaccines against TB. Here, we depleted lymphocyte subsets prior to and during Mtb challenge in i. v. BCG-vaccinated macaques to identify those necessary for protection. Depletion of adaptive CD4 T cells, but not adaptive CD8αβ T cells, resulted in loss of protection with increased Mtb burdens and dissemination, indicating that CD4 T cells are critical to i. v. BCG-mediated protection. Depletion of unconventional CD8α-expressing lymphocytes (NK cells, innate T cells, and CD4+CD8α+ double-positive T cells) abrogated protection in most i. v. BCG-immunized macaques, supporting further investigation into which of these cell subsets contribute to protection after vaccination.

Concepts Keywords
Cd4 Animals
Depletion BCG Vaccine
Mycobacterium BCG Vaccine
Tuberculosis CD4-Positive T-Lymphocytes
Vaccines CD8 Antigens
CD8 Antigens
CD8-Positive T-Lymphocytes
Lymphocyte Depletion
Macaca mulatta
Mycobacterium tuberculosis
Tuberculosis
Vaccination

Semantics

Type Source Name
drug DRUGBANK BCG vaccine
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH infection
disease IDO cell

Original Article

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