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  • Title: Coadministration of interleukins 7 and 15 with bacille Calmette-Guérin mounts enduring T cell memory response against Mycobacterium tuberculosis.
    Author: Singh V, Gowthaman U, Jain S, Parihar P, Banskar S, Gupta P, Gupta UD, Agrewala JN.
    Journal: J Infect Dis; 2010 Aug 15; 202(3):480-9. PubMed ID: 20569158.
    Abstract:
    BACKGROUND: The bacille Calmette-Guérin (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 alpha (TNF-alpha), 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-alpha, 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.
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