Caccamo Nadia, Meraviglia Serena, La Mendola Carmela, Guggino Giuliana, Dieli Francesco, Salerno Alfredo
Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy.
J Immunol. 2006 Aug 1;177(3):1780-5. doi: 10.4049/jimmunol.177.3.1780.
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-A0201 CD8 T cells in children affected by tuberculosis (TB) before and 4 mo after chemotherapy and healthy contact children. Using Ag85A peptide/HLA-A0201 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.
结核分枝杆菌感染了全球三分之一的人口，每年导致200万人死亡。由于记忆性CD8 T细胞在表型和功能特征方面表现出高度异质性，我们研究了结核病（TB）患儿在化疗前和化疗后4个月以及健康接触儿童中Ag85A表位特异性HLA-A0201 CD8 T细胞的频率、表型和功能特性。使用Ag85A肽/HLA-A0201五聚体，我们发现结核患儿治疗前血液中肽特异性CD8 T细胞的频率较低，治疗后持续增加至健康接触者中检测到的水平。对CD45RA和CCR7表面标志物表达的体外分析表明，活动性结核病期间Ag85A表位特异性CD8 T细胞的代表性存在偏差，以T中央记忆细胞为主，终末分化T细胞减少，治疗后这种情况得到逆转。因此，结核病患者的五聚体特异性CD8 T细胞产生的IFN-γ水平较低，穿孔素表达也较低，治疗后恢复。在一名结核性脑膜炎患儿的脑脊液中发现具有T效应记忆和终末分化表型的五聚体特异性CD8 T细胞频率升高，强烈表明此类CD8效应细胞在疾病部位存在分隔。我们的研究首次对结核病期间Ag特异性记忆和效应CD8 T细胞进行了表征，可能有助于了解候选疫苗应刺激何种免疫反应以实现保护。
