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

Bhattacharya, Debapriya ; Dwivedi, Ved Prakash ; Kumar, Santosh ; Reddy, Madhava C. ; Van Kaer, Luc ; Moodley, Prashini ; Das, Gobardhan (2014) Simultaneous inhibition of T helper 2 and T regulatory cell differentiation by small molecules enhances bacillus Calmette-Guerin vaccine efficacy against tuberculosis Journal of Biological Chemistry, 289 (48). pp. 33404-33411. ISSN 0021-9258

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Official URL: http://www.jbc.org/content/289/48/33404.full

Related URL: http://dx.doi.org/10.1074/jbc.M114.600452

Abstract

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.

Item Type:Article
Source:Copyright of this article belongs to American Society for Biochemistry and Molecular Biology.
Keywords:Cytokine; Immunotherapy; Mycobacterium Tuberculosis; T Helper Cells; Vaccine
ID Code:112681
Deposited On:07 Jun 2018 04:43
Last Modified:07 Jun 2018 04:43

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