Koelle D M, Reymond S N, Chen H, Kwok W W, McClurkan C, Gyaltsong T, Petersdorf E W, Rotkis W, Talley A R, Harrison D A
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
J Virol. 2000 Dec;74(23):10930-8. doi: 10.1128/jvi.74.23.10930-10938.2000.
Herpes stromal keratitis (HSK) is a prevalent and frequently vision-threatening disease associated with herpes simplex virus type 1 (HSV-1) infection. In mice, HSK progression occurs after viral clearance and requires T cells and neutrophils. One model implicates Th1-like CD4 T cells with cross-reactivity between the HSV-1 protein UL6 and a corneal autoantigen. HSK can be prevented by establishing specific immunological tolerance. However, HSK can also occur in T-cell receptor-transgenic X SCID mice lacking HSV-specific T cells. To study the pathogenesis of HSK in the natural host species, we measured local HSV-specific T-cell responses in HSK corneas removed at transplant surgery (n = 5) or control corneas (n = 2). HSV-1 DNA was detected by PCR in two specimens. HSV-specific CD4 T cells were enriched in three of the five HSK specimens and were not detectable in the control specimens. Reactivity with peptide epitopes within the tegument proteins UL21 and UL49 was documented. Responses to HSV-1 UL6 were not detected. Diverse HLA DR and DP alleles restricted these local responses. Most clones secreted gamma interferon, but not interleukin-5, in response to antigen. HSV-specific CD8 cells were also recovered. Some clones had cytotoxic-T-lymphocyte activity. The diverse specificities and HLA-restricting alleles of local virus-specific T cells in HSK are consistent with their contribution to HSK by a proinflammatory effect.
疱疹性基质性角膜炎（HSK）是一种常见且常威胁视力的疾病，与1型单纯疱疹病毒（HSV-1）感染有关。在小鼠中，HSK在病毒清除后进展，且需要T细胞和中性粒细胞。一种模型认为，具有Th1样特性的CD4 T细胞在HSV-1蛋白UL6和一种角膜自身抗原之间存在交叉反应。通过建立特异性免疫耐受可预防HSK。然而，HSK也可发生在缺乏HSV特异性T细胞的T细胞受体转基因X SCID小鼠中。为了研究HSK在天然宿主物种中的发病机制，我们检测了在移植手术时切除的HSK角膜（n = 5）或对照角膜（n = 2）中局部HSV特异性T细胞反应。通过PCR在两个标本中检测到了HSV-1 DNA。在五个HSK标本中的三个中富集了HSV特异性CD4 T细胞，而在对照标本中未检测到。记录了与被膜蛋白UL21和UL49内肽表位的反应性。未检测到对HSV-1 UL6的反应。多种HLA DR和DP等位基因限制了这些局部反应。大多数克隆在接触抗原后分泌γ干扰素，但不分泌白细胞介素-5。还回收了HSV特异性CD8细胞。一些克隆具有细胞毒性T淋巴细胞活性。HSK中局部病毒特异性T细胞的多种特异性和HLA限制等位基因与其通过促炎作用对HSK的贡献一致。
