Activated inflammatory infiltrate in HSV-1-infected corneas without herpes stromal keratitis
Activated inflammatory infiltrate in HSV-1-infected corneas without herpes stromal keratitis
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DOI：
10.1167/iovs.07-1107
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Hendricks, Robert L.
中科院分区：
文献类型：
--
作者：
Divito, Sherrie J.;Hendricks, Robert L.
PURPOSE. To investigate herpes stromal keratitis (HSK) immunopathology by studying HSV-1-infected corneas that fail to develop HSK.METHODS. Plaque assay quantified HSV-1 in the tear film of infected mice. FACS analysis enumerated corneal leukocytic infiltrate and characterized infiltrate phenotypically after staining for activation and regulatory T cell (Treg) markers and for markers of antigen-presenting cell (APC) maturation. Treg cells were depleted in vivo using anti-CD25 mAb. Luminex analysis quantified the amount of cytokines and chemokines expressed in corneal tissue homogenate.RESULTS. Infected corneas without HSK exhibited a pronounced leukocytic infiltrate containing a significantly higher proportion and nearly identical absolute number of activated CD4(+) T cells 15 days after infection when compared with those with HSK. Moreover, the frequency and absolute number of regulatory CD4(+) T cells (Tregs) was lower in nondiseased corneas, and Treg depletion did not influence HSK incidence. The frequency of mature, immunogenic DCs and the ratio of mature DCs to CD4(+) T cells were nearly identical in corneas with and without HSK. The authors observed a reduced population of neutrophils and reduced expression of neutrophil chemoattractants MIP-1 beta and keratinocyte chemoattractant and the neutrophil-attracting cytokine IL-6 in corneas without HSK.CONCLUSIONS. These findings demonstrate that HSV-1-infected corneas can retain clarity in the presence of a substantial secondary leukocytic infiltrate, that activated D4(+) T cells, while necessary, are not sufficient for HSK development, that susceptibility to HSK is not determined by Tregs, and that clinical disease correlates with the accumulation of a critical mass of neutrophils through chemoattraction.
