Unforeseen consequences of IL-12 expression in the eye of GFAP-IL12 transgenic mice following herpes simplex virus type 1 infection.
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(+) or CD8(+) cells at the time of infection. In addition, infiltration of mononuclear cells was associated with the expression of transforming growth factor-beta (TGF-beta) by cells in the cornea. Consistent with increases in tissue associated TGF-beta 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-beta1 per se because transgenic mice expressing TGF-beta1 driven by the lens-specific alphaA-crystallin promoter succumb to HSV-1 infection at a similar rate as wild-type controls.
Carr
Daniel J J
DJ
Department of Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. dan.carr@ouhsc.edu
Ash
John
J
Al-Khatib
Khaldun
K
Campbell
Iain L
IL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000502:physiology*; D018259:Herpesvirus 1, Human; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D016849:Keratitis, Herpetic / Q000378:metabolism*; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D005904:Glial Fibrillary Acidic Protein; D016212:Transforming Growth Factor beta; D018664:Interleukin-12