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.