Increased interleukin-17 production both in helper T cell subset Th17 and CD4-negative T cells in human immunodeficiency virus infection

Abstract

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)-γ 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/μL (p < 0.0001), CD8+ T cell counts (median): 875.5 versus 382.5 cells/μL (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. © Mary Ann Liebert, Inc.