人类免疫缺陷病毒感染者免疫功能重建不全的研究进展

Pathogenesis of impaired immune reconstitution in human immunodeficiency virus-infected patients

约20%的人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者在接受抗病毒治疗后,外周血CD4+T细胞水平无法有效恢复,即免疫功能重建不全,但发生机制目前尚不明确。本文根据HIV感染者的临床和免疫学指标,分析发生免疫功能重建不全的风险因素;进一步从外周循环系统中T细胞损伤、细胞因子变化及肠道黏膜局部CD4+T细胞删除等方面解析可能机制,其中肠道黏膜CD4+T细胞删除可能与肠道微生物菌群诱导的细胞焦亡有关。虽然目前国际上有多项关于免疫功能重建不全患者治疗方案的临床试验,但由于缺乏一致的、有力的基础研究证据,导致疾病诊断指标缺乏,单独细胞因子给药治疗亦未取得突破性进展。因此,应深入探索免疫功能重建不全发生机制,进行大样本、长时间的前瞻性队列研究,制定免疫功能重建不全的临床与免疫学界定标准,从而为临床治疗提供科学依据。

Approximately 20% of human immunodeficiency virus（HIV）-infected patients do not achieve optimal CD4^＋T cell recovery despite suppression of viral replication after antiretroviral（ART）treatment.These patients are referred to as immunological non-responders（INRs）.However,the mechanisms involved are incompletely understood.This review summarizes the risk factors regarding the impaired immune reconstitution in HIV infection from the perspectives of clinical and immunological indicators.The speculated mechanisms of the failure of immune recovery may be the exhaustion of CD4^＋T cells in peripheral circulation system, orchestration of cytokines and pyroptosis of CD4^＋T cells at the gastrointestinal mucosal site.Specifically,microbial flora may contribute to the pyroptosis of CD4^＋T cells at the intestinal mucosa-associated lymphoid tissue.Several clinical trials of additional treatment to ART that may improve immune reconstitution have been investigated but results thus far have proved disappointing because of the absence of medical evidence.Thus,prospective cohort study of larger samples should be conducted in future to define INRs,elucidate mechanisms and support clinical practice.