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.
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.
Authors: K F Siddiqui; M Amir; N Khan; G Rama Krishna; J A Sheikh; K Rajagopal; J N Agrewala Journal: Clin Exp Immunol Date: 2015-06-03 Impact factor: 4.330
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Authors: Souheil-Antoine Younes; George Punkosdy; Stephane Caucheteux; Tao Chen; Zvi Grossman; William E Paul Journal: PLoS Biol Date: 2011-10-11 Impact factor: 8.029
Authors: Uthaman Gowthaman; Pradeep K Rai; Weiguang Zeng; David C Jackson; Javed N Agrewala Journal: Indian J Med Res Date: 2013-11 Impact factor: 2.375