Herpes simplex virus infection of human fibroblasts and keratinocytes inhibits recognition by cloned CD8+ cytotoxic T lymphocytes.

Herpes simplex virus infection of human fibroblasts and keratinocytes inhibits recognition by cloned CD8+ cytotoxic T lymphocytes.
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人类成纤维细胞和角质形成细胞的单纯疱疹病毒感染抑制克隆的 CD8 细胞毒性 T 淋巴细胞的识别。

DOI:
10.1172/jci116317
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发表时间:
1993
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Corey,L
Corey,L
中科院分区:
--
文献类型:
--
作者:
Koelle,DM;Tigges,MA;Burke,RL;Symington,FW;Riddell,SR;Abbo,H;Corey,L

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对单纯疱疹病毒 (HSV) 具有特异性的 CD8+ 细胞毒性 T 淋巴细胞 (CTL) 克隆源自两名生殖器 HSV-2 感染的捐献者。这些 CTL 克隆特异性裂解 HSV 感染的自体 B 类淋巴母细胞,但不裂解 HSV 感染的成纤维细胞。外源肽加载使两种细胞类型都对已知特异性的 HSV 特异性 CTL 克隆的裂解敏感。 HSV 感染使成纤维细胞对肽敏化产生抵抗。 HSV 感染还使成纤维细胞和角质形成细胞对同种异体 CD8+ CTL 克隆的裂解不敏感。 HSV 感染仅略微减少了该系统中 B 类淋巴母细胞的裂解。成纤维细胞同种异体裂解的减少是剂量和时间依赖性的,并且被阿昔洛韦阻断,表明晚期HSV基因产物的参与。 HSV导致成纤维细胞表面HLA I类抗原减少,至少部分是由于重链-β2微球蛋白异二聚体的合成减少。这些结果表明,HSV 诱导的皮肤细胞对 CD8+ CTL 抗原呈递的阻断可能是 HSV 限制或逃避宿主免疫反应的机制。
CD8+ cytotoxic T lymphocytes (CTL) clones with specificity for herpes simplex virus (HSV) were derived from two donors with genital HSV-2 infection. These CTL clones specifically lysed HSV-infected autologous B lymphoblastoid cells, but not HSV-infected fibroblasts. Exogenous peptide loading sensitized both cell types to lysis by an HSV-specific CTL clone of known specificity. HSV infection rendered fibroblasts refractory to peptide sensitization. HSV infection also rendered fibroblasts and keratinocytes insensitive to lysis by allospecific CD8+ CTL clones. Lysis of B lymphoblastoid cells in this system was only slightly reduced by HSV infection. Reduction of fibroblast allospecific lysis was dose and time dependent and was blocked by acyclovir, indicating the involvement of a late HSV gene product. HSV caused a reduction of fibroblast cell surface HLA class I antigen, at least in part due to reduction of synthesis of heavy chain-beta 2 microglobulin heterodimers. These results suggest that HSV-induced blockade of antigen presentation by cutaneous cells to CD8+ CTL may be a mechanism by which HSV limits or evades the immune response of the host.Images