Vδ2⁺γδ T Cell Function inMycobacterium tuberculosis–and HIV‐1–Positive Patients in the United States and Uganda: Application of a Whole‐Blood Assay

Background. V gamma 9(+)V delta 2(+) gamma delta T cells (V delta 2(+) T cells) are activated by Mycobacterium tuberculosis and secrete interferon (IFN)-gamma. V delta 2(+) T cells recognize phosphoantigens, such as bromohydrin pyrophosphate (BrHPP), and link innate and adaptive immunity. Methods. A whole-blood assay was developed that used IFN-gamma secretion in response to BrHPP as a measurement of V delta 2(+) T cell function. Results. 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(+) T cell expansion of peripheral-blood mononuclear cells. The assay was used to evaluate V delta 2(+) 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(+) T cell response was independent of the tuberculin skin test response. In Uganda, V delta(2)+ 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(+) T cell responses. Conclusions. Tuberculosis and HIV-1 infection are associated with decreased V delta 2(+) T cell function. Decreased V delta 2(+) T cell function may contribute to increased risk for tuberculosis in HIV-1 - positive patients.