Gangappa S, Babu J S, Thomas J, Daheshia M, Rouse B T
Department of Microbiology, University of Tennessee, Knoxville 37996, USA.
J Immunol. 1998 Oct 15;161(8):4289-300.
Herpetic stromal keratitis (HSK) is a CD4+ T cell-controlled immunopathologic lesion in the eye that results from infection with herpes simplex virus (HSV). Target Ags involved in HSK remain undefined. In this study, we determined if HSK could be induced in animals genetically incapable of generating HSV Ag-specific CD4+ T cells. Mice bearing transgenic TCR specific to OVA peptide 323-339 (DO11.10) were crossed to SCID mice whose offspring (Tg-SCID) possessed CD4+ T cells, >98% of which expressed the OVA peptide-specific TCR. HSV infection of Tg-SCID mice was lethal, and mice failed to generate detectable T cell responses even after repeated immunization with a mutant avirulent virus (AN-1). Immunization with AN-1 virus followed by ocular challenge with HSV resulted in ocular inflammation before encephalitis, in contrast to the protection conferred in the control BALB/c and DO11.10 mice. These results indicate that clinical HSK may not require viral Ag recognition by CD4+ T cells and that T cells of irrelevant specificity can be recruited, activated, and driven into effector function in the HSV-infected cornea. This is suggested to represent a bystander activation effect resulting from the presence of proinflammatory mediators resulting from HSV replication.
疱疹性基质性角膜炎（HSK）是一种由单纯疱疹病毒（HSV）感染引起的、由CD4 + T细胞控制的眼部免疫病理损伤。HSK中涉及的靶抗原仍未明确。在本研究中，我们确定了在基因上无法产生HSV抗原特异性CD4 + T细胞的动物中是否能诱导出HSK。将携带针对OVA肽323 - 339的转基因TCR的小鼠（DO11.10）与SCID小鼠杂交，其后代（Tg - SCID）拥有CD4 + T细胞，其中>98%表达OVA肽特异性TCR。Tg - SCID小鼠感染HSV是致命的，即使在用突变无毒病毒（AN - 1）反复免疫后，小鼠也未能产生可检测到的T细胞反应。用AN - 1病毒免疫后再用HSV进行眼部攻击，与对照BALB/c和DO11.10小鼠所获得的保护相反，在脑炎之前会导致眼部炎症。这些结果表明，临床HSK可能不需要CD4 + T细胞识别病毒抗原，并且不相关特异性的T细胞可以在HSV感染的角膜中被募集、激活并发挥效应功能。这被认为代表了由HSV复制产生的促炎介质的存在所导致的旁观者激活效应。
