Increased interleukin-17 production both in helper T cell subset Th17 and CD4-negative T cells in human immunodeficiency virus infection.
Interleukin (IL)-17 is produced mainly by activated CD4(+) T cells, currently known as Th17. Human immunodeficiency virus (HIV) pathogenesis leads to CD4(+) T cell depletion. This is the first report of IL-17 in HIV infection. We assessed IL-17 expression in the CD4(+) T cells (Th17) of 40 asymptomatic HIV-infected treatment-naive patients compared with 40 HIV-seronegative volunteers. Peripheral blood mononuclear cells (PBMCs), with/without phorbol myristate acetate (PMA)/ionomycin stimulation, were stained with CD3, CD4, IL-17, and interferon (IFN)-gamma antibodies and analyzed by four-color flow cytometry. Both groups had comparable baseline data, except for age (mean+/-SD): 36 +/- 9 versus 30 +/- 9 yr (p= 0.001), CD4(+) T cell counts (median): 218 versus 623 cells/microL (p < 0.0001), CD8(+) T cell counts (median): 875.5 versus 382.5 cells/microL ((p) < 0.0001), and CD4(+)/CD8(+) cell ratios (median): 0.225 versus 1.45 (p< 0.0001). Without stimulation, the percentages of IL-17(+) CD3(+) CD4() and IL-17(+) CD3(+) CD4() cells among HIV-seropositive and -seronegative volunteers (median) were as follows: 0.68 versus 0.12% (p< 0.0001) and 0.92 versus 0.09% (p< 0.0001), respectively. With PMA/ionomycin stimulation, the percent IL-17 expression in CD4(+) cells (median) was 1.45 versus 0.65 (p< 0.0001) and in CD4() T cells it was 1.0 versus 0.12 (p< 0.0001). In conclusion, HIV infection is associated with a significant increase in IL-17 production in both CD4(+) and CD4() T cells in peripheral blood. IL-17 expression was further inducible by PMA/ionomycin stimulation in vitro only in CD4(+) T cells. The roles of IL-17 and Th17 in HIV viral replication and immunopathogenesis are under further investigation.
Maek-A-Nantawat
Wirach
W
Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Buranapraditkun
Supranee
S
Klaewsongkram
Jettanong
J
Ruxrungtham
Kiat
K
Ruxrungthum
Kiat
K
D000328:Adult; D015704:CD4 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D020381:Interleukin-17 / Q000032:analysis / Q000096:biosynthesis*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015704:CD4 Antigens; D020381:Interleukin-17; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate