Coadministration of interleukins 7 and 15 with Bacille Calmette-Guerin mounts enduring T cell memory response against Mycobacterium tuberculosis

Abstract

Background: The Bacille Calmette-Guerin (BCG) vaccine renders protection against tuberculosis in childhood but not in adulthood. This may be due to its failure to induce long-lasting memory T cells. T cell memory is dependent on crucial cytokine signals during the priming phases. Therefore, coadministering the BCG vaccine with cytokines may improve its efficacy. Methods: A combination of the cytokines interleukin 7 (IL-7) and interleukin 15 (IL-15) or a combination of the cytokines interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), which are known to influence memory T cell generation, were administered along with BCG to mice. The animals were rested for a period of 240 d before they were challenged with Mycobacterium tuberculosis. Five weeks later, they were killed to study the T cell memory response. Results: Administration of IL-7 and IL-15, but not IL-1, IL-6 and TNF-α, with BCG resulted in an improved CD4 and CD8 T cell memory response. Mice injected with BCG supplemented with IL-7 and IL-15 showed enhanced T cell proliferation, T helper 1-type cytokine production and an increased pool of multifunctional M. tuberculosis-specific memory T cells. Furthermore, there was a statistically significant reduction in the mycobacterial burden in the lungs. Conclusion: Our results indicate that supplementation of the BCG vaccine with IL-7 and IL-15 would substantially improve its efficacy by enhancing the T cell memory response.