CD4 T-cell deficiency and dysfunction in HIV patients receiving effective antiretroviral therapy

在接下来的5年里，全世界将有大量的人开始接受艾滋病毒感染的抗逆转录病毒治疗。这种疗法部分纠正了CD4T细胞缺陷(HIV感染引起的最典型的免疫缺陷)，但不能使治疗前免疫缺陷非常严重的患者的免疫系统恢复正常。这项研究将确定接受抗逆转录病毒药物治疗的患者残留免疫缺陷的原因，目的是引入新的治疗方法来纠正这些缺陷。我们之前的研究已经证明，接受抗逆转录病毒药物治疗的HIV患者的新T细胞的产生受到胸腺功能的影响，但这并不能解释所有新T细胞的产生。我们将调查人体内T细胞产生的其他部位。我们之前也已经证明，在成功接受抗逆转录病毒药物治疗的患者中，CD4T细胞恢复不良与免疫激活有关，即使CD4T细胞数量大幅增加，T细胞也不能充分发挥作用。我们将确定这些异常是否是单核细胞或树突状细胞激活T细胞的持续性缺陷的结果。我们的研究结果将改善艾滋病毒感染者的治疗和预期寿命。

Large numbers of people throughout the world will commence antiretroviral treatment for HIV infection over the next 5 years. This treatment partially corrects CD4 T-cell deficiency (the most characteristic immune defect caused by HIV infection) but does not restore the immune system to normal in patients who were very immunodeficient before treatment. This study will determine the cause of residual immune defects in patients receiving antiretroviral drugs with the aim of introducing new therapies to correct those defects. Our previous studies have demonstrated that the production of new T-cells in HIV patients receiving antiretroviral durgs is affected by the function of the thymus, but that this does not account for the production of all new T-cells. We will investigate other sites of T-cell production in the body. We have also previously shown that poor recovery of CD4 T-cells in patients successfully treated with antiretroviral drugs is associated with immune activation and that the T-cells do not function adequately, even when CD4 T-cell counts are substantially increased. We will determine whether these abnormalities are the result of a persistent defect in T cell activation by monocytes and-or dendritic cells. The findings of our studies will improve the treatment and life-expectancy of individuals with HIV infection.