Immunology Service, Hospital Clinic-Institut d'Investigacions Biomèdiques Augustí Pi i Suñer, University of Barcelona, Barcelona, Spain.
Clin Infect Dis. 2011 Mar 1;52(5):662-70. doi: 10.1093/cid/ciq197.
It is unknown whether a Toxoplasma gondii-specific T cell response is restored after successful combined antiretroviral therapy (cART) in patients with AIDS and current or previous toxoplasmic encephalitis (TE).
We performed a multicenter cross-sectional study with 17 healthy T. gondii-positive human immunodeficiency virus (HIV)-1-uninfected individuals and 90 patients coinfected with HIV-1 and T. gondii distributed in 5 groups according to their CD4(+) T cell counts and T. gondii infection (with or without current or previous TE). We investigated the lymphocyte proliferative response (LPR) and interferon (IFN)-γ production in response to T. gondii soluble antigen extract (SATg) and as CD4(+) and CD8(+) T cell subsets.
SATg-specific LPR and IFN-γ production were not observed in many of the most immunosuppressed patients (CD4(+) T cell count, <200 cells/μL, with or without current or previous TE). By contrast, these responses occurred in a considerable percentage (LPR, 43%; IFN-γ production, 80%) of patients receiving successful cART (CD4(+) T cell count, >200 cells/μL) who presented with TE and had already stopped secondary TE prophylaxis. Similar results were found in immunocompetent asymptomatic patients who did not receive TE prophylaxis. The predictors of SATg-specific T cell responses and IFN-γ production were a cART-mediated increase in CD4(+) T cell count and LPR to phytohemagglutinin and viral suppression and a decrease in the activated (CD38(+)) CD8(+) T cell count, respectively.
cART restores T. gondii-specific CD4 T cell responses in most patients with AIDS who had previous TE. Our data support the safety of withdrawing TE prophylaxis when the CD4(+) T cell count returns to levels >200 cells/μL.
目前尚不清楚 AIDS 患者在成功接受联合抗逆转录病毒治疗(cART)后,针对弓形虫的 T 细胞反应是否得到恢复,以及这些患者目前或既往是否患有脑弓形虫病(TE)。
我们进行了一项多中心横断面研究,共纳入 17 名健康的弓形虫阳性人类免疫缺陷病毒(HIV)-1 未感染者和 90 名 HIV-1 与弓形虫混合感染患者。这些患者根据 CD4+T 细胞计数和弓形虫感染(有无目前或既往 TE)分为 5 组。我们检测了淋巴细胞增殖反应(LPR)和干扰素(IFN)-γ产生情况,以评估其对弓形虫可溶性抗原提取物(SATg)的应答,同时检测了 CD4+和 CD8+T 细胞亚群的 IFN-γ产生情况。
在许多免疫抑制最严重的患者(CD4+T 细胞计数<200 个/μL,无论目前或既往是否存在 TE)中,并未观察到 SATg 特异性 LPR 和 IFN-γ产生。相比之下,在接受成功 cART(CD4+T 细胞计数>200 个/μL)且出现 TE 并已停止二级 TE 预防的患者中,出现了相当比例的患者(LPR:43%;IFN-γ产生:80%)存在 SATg 特异性 T 细胞反应和 IFN-γ产生。在未接受 TE 预防的免疫功能正常的无症状患者中也发现了类似的结果。SATg 特异性 T 细胞反应和 IFN-γ产生的预测因素分别为 cART 介导的 CD4+T 细胞计数增加、植物血凝素刺激的 LPR 增加、病毒抑制以及激活的(CD38+)CD8+T 细胞计数减少。
cART 可恢复大多数既往发生过 TE 的 AIDS 患者的弓形虫特异性 CD4 T 细胞反应。我们的数据支持当 CD4+T 细胞计数恢复至>200 个/μL 时,停止 TE 预防的安全性。