TY - JOUR
T1 - Blockade of the Kv1.3 K+ Channel Enhances BCG Vaccine Efficacy by Expanding Central Memory T Lymphocytes
AU - Singh, Dhiraj Kumar
AU - Dwivedi, Ved Prakash
AU - Ranganathan, Anand
AU - Bishai, William R.
AU - Van Kaer, Luc
AU - Das, Gobardhan
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Tuberculosis is the oldest known infectious disease, yet there is no effective vaccine against adult pulmonary tuberculosis. Emerging evidence indicates that T-helper 1 and T-helper 17 cells play important roles in host protection against tuberculosis. However, tuberculosis vaccine efficacy in mice is critically dependent on the balance between antigen-specific central memory T (Tcm) and effector memory T (Tem) cells. Specifically, a high Tcm/Tem cell ratio is essential for optimal vaccine efficacy. Here, we show that inhibition of Kv1.3, a potassium channel preferentially expressed by Tem cells, by Clofazimine selectively expands Tcm cells during BCG vaccination. Furthermore, mice that received clofazimine after BCG vaccination exhibited significantly enhanced resistance against tuberculosis. This superior activity against tuberculosis could be adoptively transferred to naive, syngeneic mice by CD4+ T cells. Therefore, clofazimine enhances Tcm cell expansion, which in turn provides improved vaccine efficacy. Thus, Kv1.3 blockade is a promising approach for enhancing the efficacy of the BCG vaccine in humans.
AB - Tuberculosis is the oldest known infectious disease, yet there is no effective vaccine against adult pulmonary tuberculosis. Emerging evidence indicates that T-helper 1 and T-helper 17 cells play important roles in host protection against tuberculosis. However, tuberculosis vaccine efficacy in mice is critically dependent on the balance between antigen-specific central memory T (Tcm) and effector memory T (Tem) cells. Specifically, a high Tcm/Tem cell ratio is essential for optimal vaccine efficacy. Here, we show that inhibition of Kv1.3, a potassium channel preferentially expressed by Tem cells, by Clofazimine selectively expands Tcm cells during BCG vaccination. Furthermore, mice that received clofazimine after BCG vaccination exhibited significantly enhanced resistance against tuberculosis. This superior activity against tuberculosis could be adoptively transferred to naive, syngeneic mice by CD4+ T cells. Therefore, clofazimine enhances Tcm cell expansion, which in turn provides improved vaccine efficacy. Thus, Kv1.3 blockade is a promising approach for enhancing the efficacy of the BCG vaccine in humans.
KW - BCG vaccine
KW - Kv1.3 potassium ion channel
KW - Memory T cells
KW - Mycobacterium tuberculosis
KW - clofazimine
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U2 - 10.1093/infdis/jiw395
DO - 10.1093/infdis/jiw395
M3 - Article
C2 - 27571906
AN - SCOPUS:84994741630
SN - 0022-1899
VL - 214
SP - 1456
EP - 1464
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -