Autoimmune Th2-mediated dacryoadenitis in MRL/MpJ mice becomes Th1-mediated in IL-4 deficient MRL/MpJ mice.
OBJECTIVE
MRL/MpJ mice of substrains MRL/MpJ-fas(+)/fas(+) (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (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-4(tm)/IL-4(tm) (MRL/+/IL-4(tm)) and MRL/lpr-IL-4(tm)/IL-4(tm) (MRL/lpr-IL-4(tm))-that resulted in a loss of IL-4 production were bred and evaluated for dacryoadenitis.


RESULTS
MRL/+/IL-4(tm) and MRL/lpr/IL-4(tm) 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-4(tm), 66% vs. 0.8%, P = 0.001; MRL/lpr/IL-4(tm), 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-4(tm) mice (mean difference, 28.6; P = 0.035). Greater CD86 (B7-2) than CD80 (B7-1) expression was present in MRL/+/IL-4(tm) mice (11% vs. 3%, P = 0.003) and MRL/lpr/IL-4(tm) 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.
Jabs
Douglas A
DA
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. douglas.jabs@mssm.edu
Prendergast
Robert A
RA
Campbell
Adam L
AL
Lee
Bella
B
Akpek
Esen Karamursel
EK
Gérard
Hervé C
HC
Hudson
Alan P
AP
Whittum-Hudson
Judith A
JA
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D003607:Dacryocystitis / Q000276:immunology* / Q000473:pathology; D005260:Female; D020868:Gene Silencing / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018793:Interleukin-13; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma