Autoimmune Th2-Mediated Dacryoadenitis in MRL/MpJ Mice Becomes Th1-Mediated in IL-4 Deficient MRL/MpJ Mice

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Abstract
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-γ 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-γ 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-γ 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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