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(Investigative Ophthalmology and Visual Science. 2000;41:826-831.)
© 2000 by The Association for Research in Vision and Ophthalmology, Inc.

Th1 Versus Th2 Immune Responses in Autoimmune Lacrimal Gland Disease in MRL/Mp Mice

Douglas A. Jabs1,2, Bella Lee1, Judith A. Whittum–Hudson3 and Robert A. Prendergast1

From the Departments of 1 Ophthalmology and 2 Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and the 3 Department of Medicine, Wayne State University, Detroit, Michigan.

PURPOSE. In MRL/Mp-lpr/lpr (MRL/lpr) and MRL/Mp-+/+ (MRL/+) mice, a T-cell–driven lacrimal gland inflammation spontaneously develops that is a model for Sjögren’s syndrome. The lacrimal gland lesions in these mice were evaluated by immunohistochemistry for the relative contributions of T-helper (Th)1 versus Th2 immune responses.

METHODS. Frozen sections of lacrimal glands from MRL/lpr and MRL/+ mice ages 1 through 5 months were stained with monoclonal antibodies to the cytokines interferon (IFN)-{gamma} and interleukin (IL)-4 and to the cell surface costimulatory molecules B7-1 and B7-2, which are associated with Th1 and Th2 responses, respectively.

RESULTS. The median proportion of cells staining for IL-4 ranged from 30% to 67% over time for MRL/lpr mice and from 30% to 55% for MRL/+ mice. The median proportion of cells staining for IFN-{gamma} ranged from 1% to 5% for MRL/lpr mice and from 0% to 3% for MRL/+ mice. The proportion of cells staining positively for IL-4 was significantly greater than for IFN-{gamma} in both MRL/lpr (mean difference, 33%; P = 0.0001) and MRL/+ mice (mean difference, 42%; P = 0.0002). The median proportion of cells staining positively for B7-2 ranged from 20% to 38% for MRL/lpr mice and from 16% to 34% for MRL/+ mice. The median proportion of cells staining for B7-1 ranged from 2% to 10% for MRL/lpr mice and from 2% to 5% for MRL/+ mice. The proportion of cells staining positively for B7-2 was significantly greater than for B7-1 for both MRL/lpr mice (mean difference, 15%; P = 0.001) and for MRL/+ mice (mean difference, 19%; P = 0.006).

CONCLUSIONS. On the basis of immunohistochemistry for cytokines and costimulatory molecules, inflammatory lacrimal gland lesions in MRL/lpr and MRL/+ mice appear to be a largely Th2 phenomenon.




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