Burgess Kate, Price Patricia, James Ian R, Stone Shelley F, Keane Niamh M, Lim Andrew Y F, Warmington John R, French Martyn A
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia.
J Clin Immunol. 2006 Mar;26(2):160-7. doi: 10.1007/s10875-006-9008-4. Epub 2006 Mar 28.
Extended assessments of memory T-cell responses in HIV patients who have a satisfactory virological response to combination antiretroviral therapy (CART) have been limited by availability of longitudinal samples and of antigens to which most individuals (including HIV-negative controls) have been exposed. Studies of cytomegalovirus (CMV) show that interferon-gamma (IFN-gamma) responses never recover completely, but this may be antigen-specific. Here we present responses to Candida and CMV antigens analyzed using a statistical approach that derives overall trends from samples collected at variable time points. Results were considered in relation to putative markers of T-regulatory cells. Blood mononuclear cells collected from seventeen HIV-1 patients (nadir <100 CD4 T cells/mL) 0-8 years after initiation of CART were stimulated with Candida spp lysate, Candida enolase protein or CMV lysate and production of IFN-gamma was assessed by ELISpot assay. CD4 T-cell counts increased fivefold and stabilized within 24 months on CART, following control of plasma viremia. IFN-gamma responses to Candida antigens began low and increased slowly, generating positive slope up to 60 months on CART (Candida enolase p=0.008; Candida lysate p=0.03; mixed-model Wald test). Only two patients displayed a CMV or Candida-specific IFN-gamma response above the median for seronegative controls. Proportions of T cells expressing CD25 or CD57 did not correlate with IFN-gamma responses. Slow reconstitution of IFN-gamma responses to CMV and Candida in previously immunodeficient patients with restored CD4+ T-cell counts on CART suggests a broad and nonresolving defect in memory T-cell responses.
对于接受联合抗逆转录病毒疗法（CART）后病毒学反应良好的HIV患者，记忆性T细胞反应的长期评估受到纵向样本以及大多数个体（包括HIV阴性对照）所接触抗原可用性的限制。对巨细胞病毒（CMV）的研究表明，干扰素-γ（IFN-γ）反应从未完全恢复，但这可能具有抗原特异性。在此，我们展示了使用一种统计方法分析的对念珠菌和CMV抗原的反应，该方法从在不同时间点收集的样本中得出总体趋势。结果结合T调节细胞的假定标志物进行考量。从开始CART治疗后0至8年的17名HIV-1患者（最低点<100个CD4 T细胞/毫升）采集的血液单核细胞，用念珠菌属裂解物、念珠菌烯醇化酶蛋白或CMV裂解物进行刺激，并通过ELISpot试验评估IFN-γ的产生。在血浆病毒血症得到控制后，CD4 T细胞计数在CART治疗的24个月内增加了五倍并稳定下来。对念珠菌抗原的IFN-γ反应开始较低且缓慢增加，在CART治疗长达60个月时产生正斜率（念珠菌烯醇化酶p = 0.008；念珠菌裂解物p = 0.03；混合模型Wald检验）。只有两名患者表现出高于血清阴性对照中位数的CMV或念珠菌特异性IFN-γ反应。表达CD25或CD57的T细胞比例与IFN-γ反应无关。在CART治疗中CD4 + T细胞计数恢复的先前免疫缺陷患者中，对CMV和念珠菌的IFN-γ反应重建缓慢，提示记忆性T细胞反应存在广泛且无法解决的缺陷。
