title: Blockade of the Kv1.3 K+ Channel Enhances BCG Vaccine Efficacy by Expanding Central Memory T Lymphocytes.
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.
authors: Special Centre for Molecular Medicine, Jawaharlal Nehru University, and.|International Center for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Dhiraj Kumar
authors: DK
authors: Singh
authors: Special Centre for Molecular Medicine, Jawaharlal Nehru University, and.|International Center for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Ved Prakash
authors: VP
authors: Dwivedi
authors: Special Centre for Molecular Medicine, Jawaharlal Nehru University, and.|International Center for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Anand
authors: A
authors: Ranganathan
authors: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors: William R
authors: WR
authors: Bishai
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors: Luc
authors: L
authors: Van Kaer
authors: Special Centre for Molecular Medicine, Jawaharlal Nehru University, and.
authors: Gobardhan
authors: G
authors: Das
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002991:Clofazimine / Q000627:therapeutic use; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology*; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D051664:Kv1.3 Potassium Channel; D032581:Tuberculosis Vaccines; D002991:Clofazimine
keywords: BCG vaccine; Kv1.3 potassium ion channel; Memory T cells; Mycobacterium tuberculosis; clofazimine