Kilpatrick Elizabeth D, Terajima Masanori, Koster Frederick T, Catalina Michelle D, Cruz John, Ennis Francis A
Center for Infectious Disease and Vaccine Research, and Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
J Immunol. 2004 Mar 1;172(5):3297-304. doi: 10.4049/jimmunol.172.5.3297.
We report on the role of specific CD8(+) T cells in the pathogenesis of a highly lethal human viral disease, hantavirus pulmonary syndrome (HPS). HPS is a zoonotic disease caused by transmission of Sin Nombre virus (SNV) from chronically infected deer mice. In humans, this fulminant infection is characterized by lung capillary leakage, respiratory failure, and cardiogenic shock. Individuals with HLA-B3501 have an increased risk of developing severe HPS, suggesting that CD8(+) T cell responses to SNV contribute to pathogenesis. We identified three CD8(+) T cell epitopes in SNV presented by HLA-B3501 and quantitated circulating SNV-specific CD8(+) T cells in 11 acute HPS patients using HLA/peptide tetramers. We found significantly higher frequencies of SNV-specific T cells in patients with severe HPS requiring mechanical ventilation (up to 44.2% of CD8(+) T cells) than in moderately ill HPS patients hospitalized but not requiring mechanical ventilation (up to 9.8% of CD8(+) T cells). These results imply that virus-specific CD8(+) T cells contribute to HPS disease outcome. Intense CD8(+) T cell responses to SNV may be induced by the encounter of the unnatural human host to this zoonotic virus without coevolution. This may also be the immunopathologic basis of other life-threatening human virus infections.
我们报告了特定CD8(+) T细胞在一种高度致命的人类病毒性疾病——汉坦病毒肺综合征（HPS）发病机制中的作用。HPS是一种人畜共患病，由慢性感染的鹿鼠传播辛诺柏病毒（SNV）所致。在人类中，这种暴发性感染的特征是肺毛细血管渗漏、呼吸衰竭和心源性休克。携带HLA - B3501的个体患严重HPS的风险增加，这表明CD8(+) T细胞对SNV的反应促成了发病机制。我们鉴定了由HLA - B3501呈递的SNV中的三个CD8(+) T细胞表位，并使用HLA/肽四聚体对11例急性HPS患者循环中的SNV特异性CD8(+) T细胞进行定量分析。我们发现，需要机械通气的严重HPS患者中SNV特异性T细胞的频率（高达CD8(+) T细胞的44.2%）显著高于住院但不需要机械通气的中度HPS患者（高达CD8(+) T细胞的9.8%）。这些结果表明病毒特异性CD8(+) T细胞对HPS疾病的转归有影响。对SNV强烈的CD8(+) T细胞反应可能是由于非自然的人类宿主接触这种人畜共患病毒且没有共同进化所诱导的。这也可能是其他危及生命的人类病毒感染的免疫病理基础。
