Th1 versus Th2 immune responses in autoimmune lacrimal gland disease in MRL/Mp mice

PURPOSE. In MRL/Mp-1pr/1pr (MRL/1pr) and MRL/Mp-+/+ (MRL/+) mice, a T-cell- driven lacrimal gland inflammation spontaneously develops that is a model f or Sjogren's syndrome. The lacrimal gland lesions in these mice were evalua ted by immunohistochemistry for the relative contributions of T-helper (Th) 1 versus Th2 immune responses. METHODS. Frozen sections of lacrimal glands from MRL/1pr and MRL/+ mice age s 1 through 5 months were stained with monoclonal antibodies to the cytokin es interferon (IFN)-gamma and interleukin (IL)-4 and to the cell surface co stimulatory 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% t o 67% over time for MRL/1pr mice and from 30% to 55% for MRL/+ mice. The me dian proportion of cells staining for IFN-gamma ranged from 1% to 5% for MR L/1pr mice and from 0% to 3% for MRL/+ mice. The proportion of cells staini ng positively for IL-4 was significantly greater than for IFN-gamma in both MRL/1pr (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/1pr 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/1pr mice and from 2% to 5% for MRL/+ mice. The proportion of cell s staining positively for B7-2 was significantly greater than for B7-1 for both MRL/1pr mice (mean difference, 15%; P = 0.001) and for MRL/+ mice (mea n difference, 19%; P = 0.006). CONCLUSIONS. On the basis of immunohistochemistry for cytokines and costimu latory molecules, inflammatory lacrimal gland lesions in MRL/1pr and MRL/mice appear to be a largely Th2 phenomenon.