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.
Bibliographical noteFunding Information:
The study was supported by Indian Council of Medical Research (ICMR) and Department of Biotechnology (DBT), Govt. of India, New Delhi, India.
The study was supported by Indian Council of Medical Research(ICMR) and Department of Biotechnology(DBT), Govt. of India, New Delhi, India.
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 2014 Elsevier B.V., All rights reserved.
- Effector T cells
- Natural killer T cell
- Programmed death-1
- T helper-1