Study on immune mechanisms of HAART associated immune reconstitution inflammatory syndrome in AIDS

Abstract

Objective To investigate the immunological pathogenesis of immune reconstitution inflammatory syndrome （IRIS） during highly active antiretroviral therapy（ HAART）, in this prospective cohort study we analyzed the lymphocyte subsets, lymphocyte activation, changes in regulatory T cells, and levels of Th1 and Th2 cytokines in both IRIS and non-IRIS groups. Methods Two hundred and thirty-eight AIDS patients received HAART and participated prospective research cohort for 24 weeks follow-up. Forty-seven IRIS cases and 191 non-IRIS cases were enrolled in the IRIS group or non-IRIS group respectively. Blood samples were collected in both groups at pre- and post-HAART 12 weeks, 24 weeks. Using flow cytometer to detect the immunophenotypes of lymphocyte subsets （CD4 ＋ CD45RA＋ CD62L＋, CD8＋ CD45RA＋ CD62L＋naive T cells; CD4＋ CD45RO＋, CD8＋ CD45RO＋ memory T cells）, activated T lymphocytes （CD4＋CD38 ＋, CD8 ＋ CD38 ＋ cells）, and regulatory T cell （ CD4 ＋ CD25 ＋ Foxp3 ＋ ）. Blood samples collected at pre-and post-HAART4 weeks, 12 weeks, 24 weeks and used ELISA to detect IL-2, IFN-γ, IL-4, IL-10and IL-7 cytokine serum levels. Results The percentages of CD4 ＋ and CD8 ＋ naive T cells and mlemory T cells exhibited no significant differences at the baseline, 12 weeks, 24 weeks of HAART initiation between both groups, but CD4 ＋ and CD8 ＋ memory T cells were demonstrated a trend towards to increase while compared to baseline during HAART. The percentages of CD4 ＋ and CD8 ＋ activated T cells are significantly higher at the baseline while compared to normal control and demonstrated a downward trend, but between both groups showed no significant difference. The percentages of CD4 ＋ regulatory T cell was lower in IRIS group than non-IRIS group at the baseline, 12 weeks, 24 weeks and the onset of IRIS. Th1 cytokines, IL-2 and IFN-γshowed an upward trend during HAART at the levels of IRIS group had significantly increased at 4 weeks and the onset of IRIS. Th2 cytokines, IL-4 and IL-10 showed a downward trend during HAART,and the levels of IL-10 in IRIS group had significantly decreased at 4 weeks and the onset of IRIS. IL-7 was higher than normal control at the baseline in two groups and showed a downward trend during HAART. The level of IL-7 was higher than non-IRIS group at all follow-up points. Conclusion Memory T cells appear rapid increase in the early stage of HAART and may play a significant role in the inflammatory response of IRIS. CD4 ＋ and CD8 ＋ naive T cells, memory T cells and activated T cells showed no significant difference between IRIS and non-IRIS group within 24 weeks after HAART started. There was a significant reduction in the frequency of regulatory T cells in IRIS group without obvious upward trend during HAART, suggesting that the immune suppression function of regulatory T cells in IRIS was impaired. IL-2 and IFN-γ significantly increased while IL-10 significantly decreased at 4 weeks post-HAART initiation and onset of IRIS in IRISgroup than non-IRIS group, suggested that IRIS was related to cytokines environment disorder. That is, a significant increase in inflammatory cytokines, while the relative lack of non-inflammatory cytokines. The level of IL-7 decreased gradually after HAART started, and it was higher in IRIS group when compared to non-IRIS group in the first 24 weeks after HAART started. Also IL-7 may play a role in the pathogenesis of IRIS. Key words: AIDS Highly active antiretroviral therapy Immune reconstitution inflammatory syndrome T lymphocyte subsets