title: Programmed death-1 receptor suppresses γ-IFN producing NKT cells in human tuberculosis.
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.
authors.affiliation: Department of Transplant Immunology & Immunogenetics, All India Institute of Medical Sciences, New Delhi, India. Electronic address: amaraiims@gmail.com.
authors.forename: Amar
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Aparajit Ballav
authors.initials: AB
authors.lastname: Dey
authors.affiliation: Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anant
authors.initials: A
authors.lastname: Mohan
authors.affiliation: Department of Transplant Immunology & Immunogenetics, All India Institute of Medical Sciences, New Delhi, India. Electronic address: salilmitra2@gmail.com.
authors.forename: Dipendra Kumar
authors.initials: DK
authors.lastname: Mitra
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013183:Sputum / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Effector T cells; Inteferon-gamma; Natural killer T cell; Programmed death-1; T helper-1