V delta 2 super(+) gamma delta T Cell Function in Mycobacterium tuberculosis- and HIV-1-Positive Patients in the United States and Uganda: Application of a Whole-Blood Assay

• Published in: The Journal of infectious diseases Vol. 192; no. 10; pp. 1806 - 1814
• Main Authors: Rojas, R E, Chervenak, KA, Thomas, J, Morrow, J, Nshuti, L, Zalwango, S, Mugerwa, R D, Thiel, BA, Whalen, C C, Boom, W H
• Format: Journal Article
• Language: English
• Published: 15.11.2005
• Subjects: Human immunodeficiency virus 1; Mycobacterium tuberculosis; USA; Uganda
• ISSN: 0022-1899

V gamma 9 super(+)V delta 2 super(+) gamma delta T cells (V delta 2 super(+) T cells) are activated by Mycobacterium tuberculosis and secrete Interferon (IFN)- gamma . V delta 2 super(+) T cells recognize phosphoantigens, such as bromohydrin pyrophosphate (BrHPP), and link innate and adaptive immunity. A whole-blood assay was developed that used IFN- gamma secretion in response to BrHPP as a measurement of V delta 2 super(+) T cell function. Peak IFN- gamma levels were detected after stimulating whole blood with BrHPP for 7-9 days. IFN- gamma production in whole blood in response to BrHPP paralleled IFN- gamma production and V delta 2 super(+) T cell expansion of peripheral-blood mononuclear cells. The assay was used to evaluate V delta 2 super(+) T cell function in subjects in the United States (n = 24) and Uganda (n = 178) who were or were not infected with M. tuberculosis and/or human immunodeficiency virus (HIV) type 1. When 50 mu mol/L BrHPP was used, 100% of healthy subjects produced IFN- gamma . The V delta 2 super(+) T cell response was independent of the tuberculin skin test response. In Uganda, V delta 2 super(+) T cell responses were decreased in patients with tuberculosis (n = 73) compared with responses in household contacts (n = 105). HIV-1-positive household contacts had lower responses than did HIV-1-negative household contacts. HIV-1-positive patients with tuberculosis had the lowest V delta 2 super(+) T cell responses. Tuberculosis and HIV-1 infection are associated with decreased V delta 2 super(+) T cell function. Decreased V delta 2 super(+) T cell function may contribute to increased risk for tuberculosis in HIV-1-positive patients.