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(Investigative Ophthalmology and Visual Science. 2007;48:5624-5629.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0237
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Autoimmune Th2-Mediated Dacryoadenitis in MRL/MpJ Mice Becomes Th1-Mediated in IL-4 Deficient MRL/MpJ Mice

Douglas A. Jabs,1,2,3 Robert A. Prendergast,1 Adam L. Campbell,4 Bella Lee,1 Esen Karamursel Akpek,1 Hervé C. Gérard,4 Alan P. Hudson,4 and Judith A. Whittum-Hudson4,5,6

1From the Departments of Ophthalmology and 2Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; the 3Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; and the Departments of 4Immunology and Microbiology, 5Medicine, and 6Ophthalmology, Wayne State University, Detroit, Michigan.

PURPOSE. MRL/MpJ mice of substrains MRL/MpJ-fas+/fas+ (MRL/+) and MRL/MpJ-faslpr/faslpr (MRL/lpr) spontaneously develop autoimmune dacryoadenitis and sialadenitis and are a model for the human disorder Sjögren syndrome. The dacryoadenitis in both substrains appears to be Th2 in nature, with little IFN-{gamma} and substantial IL-4 at the site of lacrimal gland inflammation.

METHODS. MRL/MpJ mice with a defective IL-4 gene—both MRL/+-IL-4tm/IL-4tm (MRL/+/IL-4tm) and MRL/lpr-IL-4tm/IL-4tm (MRL/lpr-IL-4tm)—that resulted in a loss of IL-4 production were bred and evaluated for dacryoadenitis.

RESULTS. MRL/+/IL-4tm and MRL/lpr/IL-4tm mice developed dacryoadenitis of similar onset, appearance, and severity as found in MRL/MpJ mice with an intact IL-4 gene. Immunohistochemistry examination revealed a substantially greater number of inflammatory cells staining for IFN-{gamma} than for IL-13 in the dacryoadenitis of IL-4–deficient MRL/MpJ mice (MRL/+/IL-4tm, 66% vs. 0.8%, P = 0.001; MRL/lpr/IL-4tm, 67% vs. 1.2%, P = 0.002). Real-time PCR demonstrated greater amounts of IFN-{gamma} than IL-13 mRNA relative transcripts in lacrimal glands of MRL/lpr/IL-4tm mice (mean difference, 28.6; P = 0.035). Greater CD86 (B7–2) than CD80 (B7–1) expression was present in MRL/+/IL-4tm mice (11% vs. 3%, P = 0.003) and MRL/lpr/IL-4tm mice (10% vs. 3%, P = 0.002).

CONCLUSIONS. These results suggest that a Th2 autoimmune process can be converted to a Th1 process in the absence of IL-4.






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