Distinct intracellular expression of il-17 in peripheral blood t cell of hiv-infected individuals

Abstract

Background: Il-17 is mainly produced by activated CD4+T cells and plays a role on neutrophil physiologies. HIV pathogenesis leads to CD4+T cell depletion. The incidence of recurrent bacterial infection seems increased among the advanced HIV patients. No information of IL-17 in HIV infection is currently published. Thus, the role IL-17 is warranted for investigation. Methods: Eightly (40 HIV-infected treatment naïve, 40 HIV-seronegative) volunteers were enrolled. PBMCs from fresh heparinized blood samples were stained with: CD3, CD4, IL-17 and IFN-g (internal positive control). Intracellular cytokine staining(ICCS) technique was used (with/without PMA/ionomycin stimulation) and analyzed by a 4-color flow-cytometer (Becton Dickinson Immunocytometry Systems). Results: Among the 2 groups, HIV infected and healthy volunteers: Gender: Male (50% vs 60%, p=0.37), age (mean±SD): 36±9 vs 30±9 (p=0.001), median (range) of CD4+T cell counts: 218 (32-820) vs 623 (294-1008) cells/mL (p0.0001), respectively. The direct IL-17 ICS analyses revealed a significantly higher % of both IL-17+CD3+CD4+ and IL-17+CD3+CD4-cells among HIV+ compared with HIV-negative individuals (median, range): 0.68 (0.05-4.7) vs 0.12 (0-1.05)% (p0.0001), and 0.92 (0.06-2.59) vs 0.09 (0.01-0.78)% (p0.0001), respectively. When cells were stimulated with PMA/I, the % IL-17 expression both in CD4+(1.45(0.23-7.5) vs 0.65(0.13-1.87), p0.0001, and CD-T cells (1.0(0.15-7.82) vs 0.12(0.01-0.63, p0.0001), were also significantly higher in the HIV+ group. Discussion: HIV-infection is associated with a significant increase in peripheral blood IL-17 T cells. Its production is enhanced by polyclonal activation (in vitro) and still further inducible by mitogen stimulation. The results indicate that IL-17 is activated during the chronic HIV immune activation. No evidence indicated that the IL-17 production was compromised among patients with very low CD4+ cell counts. Thus, further exploration of the roles of IL-17 on HIV viral replication and pathogenesis is warranted.