Cytokines in autoimmune lacrimal gland disease in MRL/MpJ mice.
OBJECTIVE
MRL/MpJ-+/+ (MRL/+) and MRL/MpJ-lpr/lpr (MRL/lpr) mice show spontaneous development of a T-cell-driven lacrimal gland inflammation that is a model for Sjögren syndrome. The lacrimal gland lesions in these mice were evaluated by quantitative RT-PCR for selected cytokine mRNA for the relative contributions of T-helper (Th)1 versus Th2 immune responses and by RT-PCR and immunohistochemistry for the contribution of the interleukin (IL)-2/IL-2 receptor (IL-2R) autocrine pathway.


METHODS
RNA was isolated from lacrimal glands of MRL/+ mice ages 1 to 9 months and from MRL/lpr mice ages 1 through 5 months, and competitive RT-PCR was used to quantify mRNA for the cytokines IL-2, -4, -10, and -12 and interferon (IFN)-gamma. Frozen sections of lacrimal glands from MRL/+ and MRL/lpr mice ages 2 through 5 months were stained for the IL-2R.


RESULTS
IL-2 and -12 mRNA transcripts were below the limit of detection (<10(-3) fg/pg hypoxanthine phosphoribosyl transferase gene; HPRT) in both MRL/+ and MRL/lpr mice of all ages. When detectable, IFN-gamma transcripts were present in low amounts and were below the limit of detection in most samples. IL-4 transcripts were present in 100- to 1000-fold greater amounts than IFN-gamma transcripts. IL-10 transcripts were detectable in both MRL/+ and MRL/lpr mice. IL-2R typically was detected on less than 10% of lymphocytes infiltrating lacrimal gland lesions in both substrains.


CONCLUSIONS
On the basis of RT-PCR for cytokine mRNA, autoimmune lacrimal gland lesions in MRL/+ and MRL/lpr mice appear to be largely Th2-mediated. There does not appear to be a direct role for the IL-2/IL-2R autocrine pathway within the microenvironment of the lacrimal gland.
Jabs
D A
DA
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. djabs@jhmi.edu
Prendergast
R A
RA
Rorer
E M
EM
Hudson
A P
AP
Whittum-Hudson
J A
JA
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007765:Lacrimal Apparatus / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2