The Role of IL-27 and its Receptor in the Pathogenesis of HIV/AIDS and Anti-viral Immune Response.

BACKGROUND: Cytokines have been widely demonstrated to involve in the pathogenesis of AIDS and the mechanisms of antiretroviral therapy. Interleukin 27 (IL-27) is a new member of the IL-12 cytokine family and has been shown to interfere HIV-1 virus replication with controversial findings. This study is to investigate the dynamic changes in plasma IL-27 level and cell surface IL-27 receptor expression in HIV/AIDS patients who underwent HAART. METHODS: Whole blood was collected from 34 HIV-positive/AIDS patients 0, 6, and 12 months after initiation of HAART and 27 healthy subjects. Plasma IL-27, IFN-γ, and IL-4 were measured by enzyme-linked immunosorbent assay, while peripheral blood CD3+CD4+ T cells count and the gp130 expressed CD3+CD4+cell were measured by flow cytometry. RESULTS: The plasma IL-27 concentration, IFN-γ concentration, and percentage of positive gp130 CD4 cells were significantly decreased in previously treatment-naive HIV/AIDS patients compared to healthy controls, but gradually increased 6 and 12 months after initiation of HAART. Conversely, IL-4 levels were significantly increased in treatment-naive HIV/AIDS patients compared to healthy controls, but gradually decreased 6 and 12 months after HAART. The concentrations of plasma IL-27 were positively correlated with the percentage of gp130 positive CD4 cells (r=0.438, p=0.016). Both plasma IL-27 concentration and gp130 positive cell percentage were positively associated with peripheral blood CD3+CD4+ T cell count (P<0.05 or P<0.01), but negatively associated with plasma HIV viral load (P<0.05 or P<0.01). CONCLUSION: IL-27 signaling (IL-27 and its receptor) may be involved in the pathogenesis of HIV infection and immune reconstitution in HIV/AIDS patients who underwent HAART. IL-27 may exert effects through regulating Th1 / Th2 ratio.

[Cellular HIV DNA quantitative testing and its significance in Chinese AIDS patients during 48 weeks' highly-active antiretroviral treatment].

OBJECTIVE: To observe the dynamic changes of peripheral blood T lymphocytes and monocytes, which serve as HIV-1 viral reservoirs, in Chinese HIV-infected patients receiving highly-active antiretroviral treatment (HAART) for 48 weeks and its clinical significance. METHODS: A total of 35 chronic HIV-1 infected adults initial received HAART. The peripheral blood T lymphocyte subsets counts were determined by flux cytometry at week 0, 24 and 48. Magnetic activated cell sorting was used to extract cellular DNA from monocytes and T lymphocytes purified from peripheral blood mononuclear cells. Real-time fluorescent quantitative PCR was used to detect the serum HIV RNA and HIV DNA of monocytes and T lymphocytes. SPSS 18.0 software was used to analyze the collected data. RESULTS: At week 0, 24, and 48 after initiation of HAART, HIV RNA levels of peripheral blood were (4.12 ± 1.41), ≤ 1.69, and ≤ 1.69 lg copies/ml, respectively; CD(4)(+) T cells were (196 ± 101), (321.90 ± 112) and (392 ± 127) cells/µl, respectively; HIV DNA level in T lymphocytes were (4.03 ± 0.53), (2.74 ± 1.16) and (2.45 ± 0.41) lg copies/10(6) cells respectively; while in monocytes, HIV DNA levels were (2.51 ± 0.68), (2.16 ± 0.34)and (2.03 ± 0.25)lg copies/10(6) cells. Statistical analysis revealed that HIV RNA level was negatively correlated with the CD(4)(+) T cell count through the whole trail, while positively correlated with the HIV DNA level in blood T lymphocytes and monocytes. HIV DNA level in T lymphocytes decreased more slowly than HIV DNA in monocytes. Moreover, peripheral blood CD(4)(+) T cell count was negatively associated with the HIV DNA capacity from T lymphocytes. CONCLUSIONS: Both T lymphocyte and monocyte may serve as viral reservoirs, and T lymphocyte might play a more important role as HIV reservoirs. The blood HIV RNA is correlated positively with the cellular HIV DNA, whereas, CD(4)(+) T cell count is correlated negatively with HIV DNA from lymphocytes, which suggests that HIV DNA levels in T lymphocyte might be one of indicators of AIDS progress during HAART.