Vdelta2+ gammadelta T cell function in Mycobacterium tuberculosis- and HIV-1-positive patients in the United States and Uganda: application of a whole-blood assay.
BACKGROUND
Vgamma9(+)Vdelta2(+) gammadelta T cells (Vdelta 2(+) T cells) are activated by Mycobacterium tuberculosis and secrete interferon (IFN)-gamma. Vdelta 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 Vdelta2(+) 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 Vdelta2(+) T cell expansion of peripheral-blood mononuclear cells. The assay was used to evaluate Vdelta2(+) 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 micromol/L BrHPP was used, 100% of healthy subjects produced IFN-gamma. The Vdelta2(+) T cell response was independent of the tuberculin skin test response. In Uganda, Vdelta2(+) 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 Velta2(+) T cell function. Decreased Vdelta2(+) T cell function may contribute to increased risk for tuberculosis in HIV-1-positive patients.
Rojas
Roxana E
RE
Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, OH 44106, USA. rxr38@cwru.edu
Chervenak
Keith A
KA
Thomas
Jeremy
J
Morrow
Jamila
J
Nshuti
Lorna
L
Zalwango
Sarah
S
Mugerwa
Roy D
RD
Thiel
Bonnie A
BA
Whalen
Christopher C
CC
Boom
W Henry
WH
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D011756:Diphosphates / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D014454:Uganda; D014481:United States
D011756:Diphosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; C429553:bromohydrin pyrophosphate; D007371:Interferon-gamma