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. Issue 1 (1st January 2015)

• Record Type: Journal Article
• Authors: Cruz, Andrea; Torrado, Egídio; Carmona, Jenny; Fraga, Alexandra G.; Costa, Patrício; Rodrigues, Fernando; Appelberg, Rui; Correia-Neves, Margarida; Cooper, Andrea M.; Saraiva, Margarida; Pedrosa, Jorge; Castro, António G.
• Is Part Of: Vaccine. Volume 33:Issue 1(2015)
• Page Start: 85
• Page End: 91
• Publication Date: 2015-01-01
• Subjects: Tuberculosis -- BCG vaccination -- Multifunctional CD4+ T cells -- Effector CD4+ T cells -- Memory CD4+ T cells; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2014.11.013
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Mice were vaccinated with BCG for 21 or 120 days before challenged with Mtb. Mice challenged 120 days after BCG vaccination displayed improved control of Mtb. BCG-mediated control of Mtb correlates with the IL-17 response and is independent of the magnitude of the IFN-γ response in the lung. Long-lasting control of Mtb correlates with the accumulation of CD4 + T cells producing IL-17, TNF and IL-2. 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.