T Cell Epitope Specificity and Pathogenesis of Mouse Hepatitis Virus-1-Induced Disease in Susceptible and Resistant Hosts
T Cell Epitope Specificity and Pathogenesis of Mouse Hepatitis Virus-1-Induced Disease in Susceptible and Resistant Hosts
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DOI：
10.4049/jimmunol.0902749
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发表时间：
2010-07-15
影响因子：
4.4
通讯作者：
Harty, John T.
中科院分区：
文献类型：
--
作者：
Khanolkar, Aaruni;Fulton, Ross B.;Harty, John T.
经鼻感染易感小鼠的小鼠肝炎病毒-1(MHV-1)与严重急性呼吸综合征(SARS)冠状病毒感染的人的肺部的一些重要病理特征相似。SARS的发病机制仍然知之甚少，尽管越来越多的证据表明免疫病理学可能起到重要作用。我们先前报道，获得性免疫反应在MHV-1感染耐药的B6小鼠中起着重要的保护作用，而CD4和CD8T细胞在易感C3H/HeJ和A/J小鼠鼻内感染MHV-1后的发病率和肺部病理的发生发展中起重要作用。在这项研究中，我们在MHV-1感染的敏感和耐药小鼠株中鉴定了新的CD4和CD8表位。对MHV-1敏感的C3H/HeJ小鼠可获得强健和广泛的MHV-1特异性CD4T细胞反应，而在耐药的B6小鼠中，抗原特异性CD8T细胞反应占主导地位。我们还表明，以前免疫的易感C3H/HEJ小鼠没有出现任何发病率，并且在致死剂量的MHV-1攻击后完全受到保护，尽管只产生了适度的次级T细胞反应。最后，我们证明，B6小鼠表现出的耐药性并不完全是由于广泛而有力的MHV-1特异性CD8 T细胞反应的形成，因为C3.SW-H2(B)/SNJ小鼠的MHV-1感染仍然与显著的发病率有关，这些小鼠具有同样强大的相同特异性的CD8 T细胞反应。因此，识别MHV-1的新的CD4和CD8 T细胞表位可以对SARS小鼠模型的肺T细胞反应进行高分辨率分析。《免疫学杂志》，2010,185：1132-1141。
Intranasal mouse hepatitis virus-1 (MHV-1) infection of susceptible mouse strains mimics some important pathologic features observed in the lungs of severe acute respiratory syndrome (SARS)-coronavirus-infected humans. The pathogenesis of SARS remains poorly understood, although increasing evidence suggests that immunopathology could play an important role. We previously reported that the adaptive immune response plays an important protective role in MHV-1-infected resistant B6 mice and that both CD4 and CD8 T cells play a significant role in the development of morbidity and lung pathology following intranasal MHV-1 infection of susceptible C3H/HeJ and A/J mice. In this study, we have identified novel CD4 and CD8 epitopes in MHV-1-infected susceptible and resistant strains of mice. Susceptible C3H/HeJ mice mount robust and broad MHV-1-specific CD4 T cell responses, whereas in resistant B6 mice, Ag-specific CD8 T cell responses dominate. We also show that previously immunized susceptible C3H/HeJ mice do not develop any morbidity and are completely protected following a lethal-dose MHV-1 challenge despite mounting only a modest secondary T cell response. Finally, we demonstrate that the resistance displayed by B6 mice is not solely accounted for by the elaboration of a broad and vigorous MHV-1-specific CD8 T cell response, as MHV-1 infection of C3.SW-H2(b)/SnJ mice, which mount an equally robust CD8 T cell response of the same specificity, is still associated with significant morbidity. Thus, identification of novel CD4 and CD8 T cell epitopes for MHV-1 permitted high-resolution analyses of pulmonary T cell responses in a mouse model of SARS. The Journal of Immunology, 2010, 185: 1132-1141.