Lepisto Andrew J, Frank Gregory M, Xu Min, Stuart Patrick M, Hendricks Robert L
Department of Immunology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.
Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3400-9. doi: 10.1167/iovs.05-0898.
To evaluate the role of CD4(+) T cells in the development of murine herpes stromal keratitis (HSK).
The corneas of wild-type (WT) BALB/c mice and three types of CD4-deficient BALB/c mice (CD4(-/-), CD4-depleted, CD4 and CD8 double-depleted) were infected with different doses of HSV-1 RE, and HSK incidence and severity were monitored. Corneal infiltrates were quantitatively and functionally assayed by flow cytometric analysis of individually digested diseased corneas and documented histologically.
At a relatively high infectious dose (1 x 10(5) pfu/cornea): (1) CD4-deficient and WT BALB/c mice had severe HSK with a similar incidence (80%-100%), whereas HSK did not develop in mice deficient in both CD4(+) and CD8(+) T cells; (2) neutrophils were the predominate leukocyte in the corneas of CD4-deficient and WT mice; (3) the corneas of WT mice had activated, HSV-1-specific CD4(+) T cells, but few if any CD8(+) T cells; (4) the corneas of CD4-deficient mice had activated, HSV-1-specific CD8(+) T cells; and (5) HSK in CD4-deficient mice was transient, showing loss of CD8(+) T cells at 2 to 3 weeks after infection (pi) followed by a loss of neutrophils. At a relatively low infectious dose of HSV-1 (10(3) pfu/cornea) severe HSK developed in 80% to 90% of WT mice, but in only 30% to 40% of CD4-deficient mice.
CD4(+) T cells preferentially mediate HSK, but, in their absence, a high infectious dose of HSV-1 can induce histologically similar but transient HSK that is mediated by CD8(+) T cells.
评估CD4(+) T细胞在小鼠疱疹性基质性角膜炎（HSK）发病过程中的作用。
用不同剂量的单纯疱疹病毒1型RE（HSV-1 RE）感染野生型（WT）BALB/c小鼠及三种CD4缺陷型BALB/c小鼠（CD4(-/-)、CD4耗竭型、CD4和CD8双耗竭型）的角膜，监测HSK的发病率和严重程度。通过对单个消化的患病角膜进行流式细胞术分析，对角膜浸润细胞进行定量和功能分析，并进行组织学记录。
在相对高的感染剂量（1×10(5) 空斑形成单位/角膜）下：（1）CD4缺陷型和WT BALB/c小鼠发生严重HSK，发病率相似（80%-100%），而CD4(+)和CD8(+) T细胞均缺陷的小鼠未发生HSK；（2）中性粒细胞是CD4缺陷型和WT小鼠角膜中主要的白细胞；（3）WT小鼠角膜中有活化的、HSV-1特异性的CD4(+) T细胞，但几乎没有CD8(+) T细胞；（4）CD4缺陷型小鼠角膜中有活化的、HSV-1特异性的CD8(+) T细胞；（5）CD4缺陷型小鼠的HSK是短暂的，感染后（pi）2至3周时CD8(+) T细胞减少，随后中性粒细胞减少。在相对低的HSV-1感染剂量（10(3) 空斑形成单位/角膜）下，80%至90%的WT小鼠发生严重HSK，但CD4缺陷型小鼠中只有30%至40%发生。
CD4(+) T细胞优先介导HSK，但在其缺失时，高感染剂量的HSV-1可诱导组织学上相似但短暂的HSK，由CD8(+) T细胞介导。
