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Updated: Aug 6, 2026
Recurrent Herpetic Stromal Keratitis in Mice, a Model for Studying Human HSK
Published on: December 18, 2012
CD8 T cells mediate transient herpes stromal keratitis in CD4-deficient mice
Andrew J Lepisto1, Gregory M Frank, Min Xu
1Department of Immunology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.
Purpose:
To evaluate the role of CD4(+) T cells in the development of murine herpes stromal keratitis (HSK).
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
CD4(+) T cells drive herpes stromal keratitis (HSK). In their absence, CD8(+) T cells can cause transient HSK, particularly at high HSV-1 doses, impacting immune responses in eye infections.
Area of Science:
- Immunology
- Ophthalmology
- Virology
Background:
- Herpes simplex virus type 1 (HSV-1) infection can lead to herpes stromal keratitis (HSK), a significant cause of blindness.
- The role of specific T cell subsets, particularly CD4(+) T cells, in HSK pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the specific contribution of CD4(+) T cells in the development and severity of murine HSK.
- To understand the compensatory mechanisms involving other immune cells, like CD8(+) T cells, in the absence of CD4(+) T cells.
Main Methods:
- Utilized wild-type (WT) and various CD4-deficient (CD4(-/-), CD4-depleted, CD4/CD8 double-depleted) BALB/c mouse models.
- Infected mice with different doses of HSV-1 and monitored HSK incidence and severity.
- Analyzed corneal immune cell infiltrates using flow cytometry and histological examination.
Main Results:
- CD4(+) T cells were found to preferentially mediate HSK in WT mice.
- In CD4-deficient mice, a high dose of HSV-1 induced a transient HSK mediated by CD8(+) T cells and neutrophils.
- HSK severity was dose-dependent and influenced by the presence or absence of specific T cell populations.
Conclusions:
- CD4(+) T cells play a primary role in the pathogenesis of HSK.
- CD8(+) T cells can mediate a less severe, transient form of HSK in the absence of CD4(+) T cells, especially following high-dose HSV-1 infection.
- Understanding T cell subset roles is crucial for developing targeted therapies for HSK.
