Programmed death-1 receptor suppresses γ-IFN producing NKT cells in human tuberculosis

Amar Singh, Aparajit Ballav Dey, Anant Mohan, Dipendra Kumar Mitra

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

IFN-γ biased Th1 effector immune response is crucial for containment of Mycobacterium tuberculosis infection. Various T cell subsets with regulatory function dictate the generation of Th1 like cells. NKT cells are a specialized T cell subset known to be activated early in immune response and control T cell response via release of immunoregulatory cytokines like IFN-γ, IL-4 and IL-10. M. tuberculosis, with abundance of its cell wall lipids may potently activate NKT cells resulting in cytokine production and PD-1 expression. In this study, among 49 treatment naive active pulmonary tuberculosis patients, we found a higher percentage of PD1+ NKT cells correlating with sputum bacillary load. Furthermore, blocking PD-1 increased the number of IFN-γ producing NKT cells by inhibiting their apoptosis. Moreover, peripheral frequency of NKT cells declined with therapy suggesting their role in host T cell response. In this study, we concluded that PD-1 preferentially induces apoptosis of IFN-γ producing NKT cells while sparing NKT cells that produce IL-4. Such a polarized NKT cell function may impose a Th2 bias on the ensuing effector T cell response leading to inefficient clearance of M. tuberculosis. Inhibiting PD-1 may therefore alter the T cell response in favor of the host by rescuing type 1 NKT cells from apoptosis and boosting Th1 effector T cell functions against M. tuberculosis.

Original languageEnglish (US)
Pages (from-to)197-206
Number of pages10
JournalTuberculosis
Volume94
Issue number3
DOIs
StatePublished - May 2014

Bibliographical note

Funding Information:
The study was supported by Indian Council of Medical Research (ICMR) and Department of Biotechnology (DBT), Govt. of India, New Delhi, India.

Funding Information:
The study was supported by Indian Council of Medical Research(ICMR) and Department of Biotechnology(DBT), Govt. of India, New Delhi, India.

Funding Information:
The authors thank all the patients and control subjects who voluntarily agreed to participate in this study. This work was supported by Department of Biotechnology & Indian Council of Medical Research Grant, Government of India. We are thankful to Drs. Ambak Rai and Ankit Saxena (Department of TI&I, AIIMS, New Delhi, India) for critical reading of this manuscript. We would like to thank Dr. U. Sengupta, (JALMA, Agra, India) for a kind gift of M. tuberculosis antigen.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Keywords

  • Effector T cells
  • Inteferon-gamma
  • Natural killer T cell
  • Programmed death-1
  • T helper-1

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