Ankersmit H J, Tugulea S, Spanier T, Weinberg A D, Artrip J H, Burke E M, Flannery M, Mancini D, Rose E A, Edwards N M, Oz M C, Itescu S
Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Lancet. 1999 Aug 14;354(9178):550-5. doi: 10.1016/s0140-6736(98)10359-8.
Cardiac transplantation is a limited option for end-stage heart failure because of the shortage of donor organs. Left-ventricular assist devices (LVADs) are currently under investigation as permanent therapy for end-stage heart failure, but long-term successful device implantation is limited because of a high rate of serious infections. To examine the relation between LVAD-related infection and host immunity, we investigated immune responses in LVAD recipients.
We compared the rate of candidal infection in 78 patients with New York Heart Association class IV heart failure who received either an LVAD (n=40) or medical management (controls, n=38). Fluorochrome-labelled monoclonal antibodies were used in analyses of T-cell phenotype. Analysis of T-cell function included intradermal responses to recall antigens and proliferative responses after stimulation by phytohaemagglutinin, monoclonal antibodies to CD3, and mixed lymphocyte culture. We measured T-cell apoptosis in vivo by annexin V binding, and confirmed the result by assessment of DNA fragmentation. Activation-induced T-cell death was measured after T-cell stimulation with antibodies to CD3. All immunological tests were done at least 1 month after LVAD implantation. Between-group comparisons were by Kaplan-Meier actuarial analysis and Student's t test.
By 3 months after implantation of LVAD, the risk of developing candidal infection was 28% in LVAD recipients, compared with 3% in controls (p=0.003). LVAD recipients had cutaneous anergy to recall antigens and lower (<70%) T-cell proliferative responses than controls after activation via the T-cell receptor complex (p<0.001). T cells from LVAD recipients had higher surface expression of CD95 (Fas) (p<0.001) and a higher rate of spontaneous apoptosis (p<0.001) than controls. Moreover, after stimulation with antibodies to CD3, CD4 T-cell death increased by 3.2-fold in LVAD recipients compared with only 1.2-fold in controls (p<0.05).
LVAD implantation results in an aberrant state of T-cell activation, heightened susceptibility of CD4 T cells to activation-induced cell death, progressive defects in cellular immunity, and increased risk of opportunistic infection.
由于供体器官短缺，心脏移植对于终末期心力衰竭而言是一种有限的选择。左心室辅助装置（LVAD）目前正作为终末期心力衰竭的永久性治疗方法进行研究，但由于严重感染发生率高，长期成功植入该装置受到限制。为了研究LVAD相关感染与宿主免疫之间的关系，我们调查了LVAD接受者的免疫反应。
我们比较了78例纽约心脏协会IV级心力衰竭患者的念珠菌感染率，这些患者接受了LVAD（n = 40）或药物治疗（对照组，n = 38）。荧光标记的单克隆抗体用于T细胞表型分析。T细胞功能分析包括对回忆抗原的皮内反应以及在受到植物血凝素、抗CD3单克隆抗体和混合淋巴细胞培养刺激后的增殖反应。我们通过膜联蛋白V结合在体内测量T细胞凋亡，并通过评估DNA片段化来确认结果。在用抗CD3抗体刺激T细胞后测量活化诱导的T细胞死亡。所有免疫测试均在LVAD植入后至少1个月进行。组间比较采用Kaplan-Meier精算分析和Student t检验。
LVAD植入后3个月时，LVAD接受者发生念珠菌感染的风险为28%，而对照组为3%（p = 0.003）。LVAD接受者对回忆抗原有皮肤无反应性，并且在通过T细胞受体复合物激活后，其T细胞增殖反应低于对照组（<70%）（p < 0.001）。与对照组相比，LVAD接受者的T细胞表面CD95（Fas）表达更高（p < 0.001），自发凋亡率更高（p < 0.001）。此外，在用抗CD3抗体刺激后，LVAD接受者的CD4 T细胞死亡增加了3.2倍，而对照组仅增加了1.2倍（p < 0.05）。
LVAD植入导致T细胞活化异常、CD4 T细胞对活化诱导的细胞死亡敏感性增加、细胞免疫逐渐缺陷以及机会性感染风险增加。
