In Vitro Immunomodulation of a Whole Blood IFN-γ Release Assay Enhances T Cell Responses in Subjects with Latent Tuberculosis Infection

• Published in: PloS one Vol. 7; no. 10; p. e48027
• Main Authors: Gaur, Rajiv L., Suhosk, Megan M., Banaei, Niaz
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.10.2012; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Adjuvants; Adolescent; Adult; Aged; Aminoquinolines - immunology; Aminoquinolines - pharmacology; Antigen-presenting cells; Antigens; Assaying; Biology; Blood; Cell activation; Costimulator; Cytokines; Epidemics; Female; Humans; Imiquimod; Immune response; Immune system; Immunity; Immunomodulation; Immunotherapy; In vitro methods and tests; Infections; Infectious diseases; Inflammation; Innate immunity; Interferon; Interferon-gamma - blood; Interferon-gamma - immunology; Interferon-gamma Release Tests - methods; Laboratories; Latent Tuberculosis - blood; Latent Tuberculosis - diagnosis; Latent Tuberculosis - immunology; Ligands; Lipopolysaccharides; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; Lymphocytes; Lymphocytes T; Male; Medicine; Middle Aged; Mycobacterium tuberculosis; Poly (I:C); Poly I-C - immunology; Poly I-C - pharmacology; Polyinosinic:polycytidylic acid; Proteins; Receptors; Reproducibility of Results; Sensitivity; Sensitivity and Specificity; Sensitivity enhancement; Studies; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Toll-like receptors; Toll-Like Receptors - agonists; Toll-Like Receptors - immunology; Tuberculosis; Viral infections; Young Adult; γ-Interferon; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048027

Activation of innate immunity via pathogen recognition receptors (PRR) modulates adaptive immune responses. PRR ligands are being exploited as vaccine adjuvants and as therapeutics, but their utility in diagnostics has not been explored. Interferon-gamma (IFN-γ) release assays (IGRAs) are functional T cell assays used to diagnose latent tuberculosis infection (LTBI); however, novel approaches are needed to improve their sensitivity. In vitro immunomodulation of a whole blood IGRA (QuantiFERON®-TB GOLD In-Tube) with Toll-like receptor agonists poly(I:C), LPS, and imiquimod was performed on blood from subjects with LTBI and negative controls. In vitro immunomodulation significantly enhanced the response of T cells stimulated with M. tuberculosis antigens from subjects with LTBI but not from uninfected controls. Immunomodulation of IGRA revealed T cell responses in subjects with LTBI whose T cells otherwise do not respond to in vitro stimulation with antigens alone. Similar to their in vivo functions, addition of poly(I:C) and LPS to whole blood induced secretion of inflammatory cytokines and IFN-α and enhanced the surface expression of antigen presenting and costimulatory molecules on antigen presenting cells. In vitro immunomodulation of whole blood IGRA may be an effective strategy for enhancing the sensitivity of T cells for diagnosis of LTBI.