Phenotypical and functional analysis of memory and effector human CD8 T cells specific for mycobacterial antigens
Phenotypical and functional analysis of memory and effector human CD8 T cells specific for mycobacterial antigens
复制标题
DOI：
10.4049/jimmunol.177.3.1780
复制
发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Salerno, Alfredo
中科院分区：
文献类型：
--
作者：
Caccamo, Nadia;Meraviglia, Serena;Salerno, Alfredo
结核分枝杆菌感染了全球人口的三分之一，每年夺去了200万人的生命。由于记忆CD8 T细胞在表型和功能特征方面表现出很高的异质性，因此我们研究了受结核病（TB）影响的儿童的AG85A表源特异性HLA-A*0201 CD8 T细胞的频率，表型和功能特性。化疗后4个月和健康接触儿童。使用AG85A肽/HLA-A*0201 Pentamer，我们发现治疗前结核病儿童中血液肽特异性的CD8 T细胞的频率低，在治疗后，在健康接触中检测到的水平始终将其升高到健康接触水平。对CD45RA和CCR7表面标记的表达的外体分析表明，在活性TB期间，AG85A表位特异性CD8 T细胞的偏斜表示，T中心记忆细胞占主导地位，终止分化的T细胞的占主导地位，在治疗后降低了治疗后的T细胞。因此，来自结核病患者的五聚体特异性CD8 T细胞产生了低水平的IFN-gamma，并且在治疗后恢复了perforin的表达较低。在疾病部位强烈表明，在脑脊液中，发现具有T效应记忆的五聚体特异性CD8 T细胞的频率升高，并发现了脑脊液中末端分化的表型，这表明疾病部位的这种CD8效应子的分裂表明。我们的研究代表了TB期间Ag特异性记忆和效应子CD8 T细胞的首次表征，并且可能有助于了解候选疫苗应刺激以实现保护的免疫反应类型。
Mycobacterium tuberculosis infects one-third of the global population and claims two million lives every year. Because memory CD8 T cells exhibit a high heterogeneity in terms of phenotype and functional characteristic, we investigated the frequency, phenotype, and functional properties of Ag85A epitope-specific HLA-A*0201 CD8 T cells in children affected by tuberculosis (TB) before and 4 mo after chemotherapy and healthy contact children. Using Ag85A peptide/HLA-A*0201 pentamer, we found a low frequency of blood peptide-specific CD8 T cells in tuberculous children before therapy, which consistently increased after therapy to levels detected in healthy contacts. Ex vivo analysis of the expression of CD45RA and CCR7 surface markers indicated a skewed representation of Ag85A epitope-specific CD8 T cells during active TB, with a predominance of T central memory cells and a decrease of terminally differentiated T cells, which was reversed after therapy. Accordingly, pentamer-specific CD8 T cells from tuberculous patients produced low levels of IFN-gamma and had low expression of perforin, which recovered after therapy. The finding of an elevated frequency of pentamer-specific CD8 T cells with T effector memory and terminally differentiated phenotypes in the cerebrospinal fluid of a child with tuberculous meningitis strongly indicates compartmentalization of such CD8 effectors at the site of disease. Our study represents the first characterization of Ag-specific memory and effector CD8 T cells during TB and may help to understand the type of immune response that vaccine candidates should stimulate to achieve protection.