Related Experiment Videos
[Inhibition by CTLA-4Ig on herpetic stromal keratitis in a murine model]
Li-kun Xia1, Jin-song Zhang, Hong Shu
1Department of Ophthalmology, The Second Affiliated Hospital, China Medical University, Shenyang 110004, China. xialk@online.ln.cn
Objective:
To investigate the inhibition by CTLA-4Ig on herpetic stromal keratitis (HSK).
Methods:
BALB/c mice infected with HSV-1 Mckrae strain by corneal scarification were injected intraperitoneally with murine CTLA-4Ig given on days 0, +2, +4 after the infection. The effects of CTLA-4Ig on HSK were evaluated.
Results:
As measured by flow cytometry, in the mice treated with CTLA-4Ig, 81.6% of CD4(+)T cells and 67.9% of CD8(+)T cells were reduced. CTLA-4Ig halted the onset of HSK, reduced the corneal stromal opacification of HSK, prevented extensive cellular infiltration in cornea, impaired the delayed type hypersensitivity and inhibited splenocytes producing Th1 cytokines.
Conclusions:
The results provide evidence that blockade of B7:CD28/CTLA-4 costimulation by CTLA-4Ig can inhibit the proliferation of T cells and Th1 response and impair onset and severity of HSK.
Insights
Cytotoxic T-lymphocyte-associated protein 4-Ig (CTLA-4Ig) effectively inhibits herpetic stromal keratitis (HSK) by reducing T-cell proliferation and Th1 responses, thereby mitigating disease severity.
Area of Science:
- Immunology
- Ophthalmology
- Virology
Context:
- Herpetic stromal keratitis (HSK) is a significant cause of vision loss.
- T-cell mediated immune responses play a crucial role in HSK pathogenesis.
- Costimulatory pathways, including B7:CD28/CTLA-4, regulate T-cell activation.
Purpose:
- To evaluate the therapeutic potential of CTLA-4Ig in a murine model of HSK.
- To investigate the impact of CTLA-4Ig on T-cell populations and cytokine production in HSK.
Summary:
- Treatment with murine CTLA-4Ig in HSV-1 infected BALB/c mice significantly reduced CD4(+) and CD8(+) T-cell populations.
- CTLA-4Ig administration halted HSK onset, decreased corneal opacification, and prevented cellular infiltration.
- The treatment inhibited delayed-type hypersensitivity and suppressed Th1 cytokine production by splenocytes.
Impact:
- CTLA-4Ig demonstrates efficacy in controlling HSK by modulating T-cell responses.
- Blocking the B7:CD28/CTLA-4 costimulatory pathway offers a potential therapeutic strategy for HSK.
- These findings support the role of CTLA-4Ig in managing viral-induced ocular inflammation.