Simultaneous inhibition of T helper 2 and T regulatory cell differentiation by small molecules enhances Bacillus Calmette-Guerin vaccine efficacy against tuberculosis.

Bhattacharya D, Dwivedi VP, Kumar S, Reddy MC, Van Kaer L, Moodley P, Das G
J Biol Chem. 2014 289 (48): 33404-11

PMID: 25315774 · PMCID: PMC4246096 · DOI:10.1074/jbc.M114.600452

Tuberculosis affects nine million individuals and kills almost two million people every year. The only vaccine available, Bacillus Calmette-Guerin (BCG), has been used since its inception in 1921. Although BCG induces host-protective T helper 1 (Th1) cell immune responses, which play a central role in host protection, its efficacy is unsatisfactory, suggesting that additional methods to enhance protective immune responses are needed. Recently we have shown that simultaneous inhibition of Th2 cells and Tregs by using the pharmacological inhibitors suplatast tosylate and D4476, respectively, dramatically enhances Mycobacterium tuberculosis clearance and induces superior Th1 responses. Here we show that treatment with these two drugs during BCG vaccination dramatically improves vaccine efficacy. Furthermore, we demonstrate that these drugs induce a shift in the development of T cell memory, favoring central memory T (Tcm) cell responses over effector memory T (Tem) cell responses. Collectively, our findings provide evidence that simultaneous inhibition of Th2 cells and Tregs during BCG vaccination promotes vaccine efficacy.

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

MeSH Terms (15)

Animals Anti-Allergic Agents Arylsulfonates Benzamides Cell Differentiation Imidazoles Mice Mice, Inbred BALB C Mycobacterium bovis Mycobacterium tuberculosis Sulfonium Compounds T-Lymphocytes, Regulatory Th2 Cells Tuberculosis, Pulmonary Tuberculosis Vaccines

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