Blockade of the Kv1.3 K+ Channel Enhances BCG Vaccine Efficacy by Expanding Central Memory T Lymphocytes

Dhiraj Kumar Singh, Ved Prakash Dwivedi, Anand Ranganathan, William Ramses Bishai, Luc Van Kaer, Gobardhan Das

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1456-1464
Number of pages9
JournalJournal of Infectious Diseases
Volume214
Issue number9
DOIs
StatePublished - Nov 1 2016

Fingerprint

BCG Vaccine
Clofazimine
Tuberculosis
T-Lymphocytes
Vaccines
Mycobacterium bovis
Kv1.3 Potassium Channel
Vaccination
Tuberculosis Vaccines
Th17 Cells
Pulmonary Tuberculosis
Communicable Diseases
Antigens

Keywords

  • BCG vaccine
  • clofazimine
  • Kv1.3 potassium ion channel
  • Memory T cells
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Blockade of the Kv1.3 K+ Channel Enhances BCG Vaccine Efficacy by Expanding Central Memory T Lymphocytes. / Singh, Dhiraj Kumar; Dwivedi, Ved Prakash; Ranganathan, Anand; Bishai, William Ramses; Van Kaer, Luc; Das, Gobardhan.

In: Journal of Infectious Diseases, Vol. 214, No. 9, 01.11.2016, p. 1456-1464.

Research output: Contribution to journalArticle

Singh, Dhiraj Kumar ; Dwivedi, Ved Prakash ; Ranganathan, Anand ; Bishai, William Ramses ; Van Kaer, Luc ; Das, Gobardhan. / Blockade of the Kv1.3 K+ Channel Enhances BCG Vaccine Efficacy by Expanding Central Memory T Lymphocytes. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 9. pp. 1456-1464.
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