Unforeseen Consequences of IL-12 Expression in the Eye of GFAP-IL12 Transgenic Mice Following Herpes Simplex Virus Type 1 Infection

Carr, Daniel J.J.; Ash, John; Al-Khatib, Khaldun; Campbell, Iain L.
May 2002
DNA & Cell Biology;May2002, Vol. 21 Issue 5/6, p467
Academic Journal
Transgenic mice expressing interleukin-12 (IL-12) under the glial fibrillary acidic protein (GFAP) promoter were evaluated for their sensitivity to herpes simplex virus type 1 (HSV-1) infection of the cornea. There was a modest but significant decrease in the infiltration of mononuclear cells in the cornea of the GFAP-IL12 transgenic mice compared to the wild-type controls during the acute stage of infection. However, during the latent stage of infection (i.e., day 30 postinfection) GFAP-IL12 transgenic mice had significantly more infiltrating cells in the corneal stroma compared to the wild-type controls. The infiltration was exacerbated by depleting transgenic mice of either CD4[sup +] or CD8[sup +] cells at the time of infection. In addition, infiltration of mononuclear cells was associated with the expression of transforming growth factor-β (TGF-β) by cells in the cornea. Consistent with increases in tissue associated TGF-β was the presence of anterior subcapsular cataracts in the GFAP-IL12 transgenic mice. Although the GFAP-IL12 transgenic mice are highly resistant to HSV-1 infection in the eye, this resistance is not related to local expression of TGF-β1 per se because transgenic mice expressing TGF-β1 driven by the lens-specific αA-crystallin promoter succumb to HSV-1 infection at a similar rate as wild-type controls.


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