Clute Shalyn C, Watkin Levi B, Cornberg Markus, Naumov Yuri N, Sullivan John L, Luzuriaga Katherine, Welsh Raymond M, Selin Liisa K
Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
J Clin Invest. 2005 Dec;115(12):3602-12. doi: 10.1172/JCI25078. Epub 2005 Nov 23.
The marked proliferation of activated CD8+ T cells is pathognomonic of EBV-associated infectious mononucleosis (IM), common in young adults. Since the diversity and size of the memory CD8+ T cell population increase with age, we questioned whether IM was mediated by the reactivation of memory CD8+ T cells specific to previously encountered pathogens but cross-reactive with EBV. Of 8 HLA-A2+ IM patients, 5 had activated T cells specific to another common virus, as evidenced by a significantly higher number of peripheral blood influenza A virus M1(58-66)-specific T cells compared with healthy immune donors. Two patients with an augmented M1 response had tetramer-defined cross-reactive cells recognizing influenza M1 and EBV-BMLF1(280-288), which accounted for up to one-third of their BMLF1-specific population and likely contributed to a skewed M1-specific T cell receptor repertoire. These epitopes, with only 33% sequence similarity, mediated differential effects on the function of the cross-reactive T cells, which may contribute to alterations in disease outcome. EBV could potentially encode an extensive pool of T cell epitopes that activate other cross-reactive memory T cells. Our results support the concept that cross-reactive memory CD8+ T cells activated by EBV contribute to the characteristic lymphoproliferation of IM.
活化的CD8 + T细胞显著增殖是EB病毒相关传染性单核细胞增多症（IM）的特征，在年轻人中常见。由于记忆CD8 + T细胞群体的多样性和大小随年龄增长而增加，我们质疑IM是否由对先前遇到的病原体特异但与EB病毒交叉反应的记忆CD8 + T细胞的重新激活介导。在8名HLA-A2 + IM患者中，5名具有对另一种常见病毒特异的活化T细胞，与健康免疫供体相比，外周血甲型流感病毒M1（58 - 66）特异的T细胞数量显著更高证明了这一点。两名M1反应增强的患者具有四聚体定义的交叉反应性细胞，可识别流感M1和EB病毒BMLF1（280 - 288），这占其BMLF1特异性群体的三分之一，可能导致M1特异性T细胞受体库的偏差。这些表位仅具有33%的序列相似性，对交叉反应性T细胞的功能产生不同影响，这可能导致疾病结局的改变。EB病毒可能潜在地编码大量激活其他交叉反应性记忆T细胞的T细胞表位。我们的结果支持这样的概念，即由EB病毒激活的交叉反应性记忆CD8 + T细胞促成了IM的特征性淋巴细胞增殖。
