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Vaccine. 2015 Jan 1;33(1):85-91. doi: 10.1016/j.vaccine.2014.11.013. Epub 2014 Nov 20.

BCG vaccination-induced long-lasting control of Mycobacterium tuberculosis correlates with the accumulation of a novel population of CD4⁺IL-17⁺TNF⁺IL-2⁺ T cells.

Author information

1
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
2
Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal.
3
Trudeau Institute, Saranac Lake, NY 12983, United States.
4
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: acastro@ecsaude.uminho.pt.

Abstract

Mycobacterium bovis Bacille Calmette-Guerin (BCG) is the only vaccine in use to prevent Mycobacterium tuberculosis (Mtb) infection. Here we analyzed the protective efficacy of BCG against Mtb challenges 21 or 120 days after vaccination. Only after 120 days post-vaccination were mice able to efficiently induce early Mtb growth arrest and maintain long-lasting control of Mtb. This protection correlated with the accumulation of CD4(+) T cells expressing IL-17(+)TNF(+)IL-2(+). In contrast, mice challenged with Mtb 21 days after BCG vaccination exhibited only a mild and transient protection, associated with the accumulation of CD4(+) T cells that were mostly IFN-γ(+)TNF(+) and to a lesser extent IFN-γ(+)TNF(+)IL-2(+). These data suggest that the memory response generated by BCG vaccination is functionally distinct depending upon the temporal proximity to BCG vaccination. Understanding how these responses are generated and maintained is critical for the development of novel vaccination strategies against tuberculosis.

KEYWORDS:

BCG vaccination; Effector CD4(+) T cells; Memory CD4(+) T cells; Multifunctional CD4(+) T cells; Tuberculosis

PMID:
25448107
DOI:
10.1016/j.vaccine.2014.11.013
[Indexed for MEDLINE]

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