Work from our group has suggested that the lacrimal gland lesions in both MRL/+ and MRL/lpr mice are predominantly Th2 in nature.
10 11 Competitive RT-PCR demonstrated that IL-4 transcripts were present in 100- to 1000-fold greater amounts than IFN-γ transcripts in both MRL/+ and MRL/lpr mice at all time points. In MRL/+ mice IL-4 transcripts increased approximately 10-fold with increasing age, whereas IFN-γ transcripts often were at the lower limit of detection. In MRL/lpr mice IL-4 transcripts increased approximately 15-fold with increasing age, whereas IFN-γ transcripts often were undetectable. In both MRL/+ and MRL/lpr mice, IL-10 transcripts increased with age, increasing approximately 15- and 100-fold, respectively, whereas IL-2 and -12 transcripts were below the limit of detection.
11 These results were supported by immunohistochemistry, which demonstrated a 10- to 20-fold greater proportion of cells staining for IL-4 than for IFN-γ in the lacrimal gland lesions of both substrains and that IFN-γ was detected on 5% or less of the inflammatory cells. B7-1 (CD80) and B7-2 (CD86) are costimulatory molecules, expressed on antigen-presenting cells, which appear to stimulate Th1 and Th2 responses, respectively. Immunohistochemistry of MRL/MpJ mice also revealed greater expression of B7-2 than B7-1. In both substrains, B7-1 was present on 10% or less of the inflammatory cells and the mean difference between the proportion of cells staining for B7-2 and B7-1 was 19% in MRL/+ mice (
P = 0.006) and 15% in MRL/lpr mice (
P = 0.0001).
10 Collectively, these data suggest that the lacrimal gland lesions in both MRL/+ and MRL/lpr were predominantly Th2 in nature. Although Th1 responses typically are associated with tissue damage, Th2 responses also can cause tissue inflammation
25 and can produce tissue damage, as demonstrated by the vascular and renal lesions in Palmerston-North mice,
26 and by experimental autoimmune uveitis in IFN-γ-deficient mice.
27 Data on lymphocyte apoptosis
28 suggest that cellular trafficking may be essential in the pathogenesis of lacrimal gland inflammation in the MRL/MpJ mice. Therefore, we sought to evaluate the chemokines present in the lacrimal glands. Because of our cytokine results, we hypothesized that those chemokines associated with a Th2 response were more likely to be upregulated than those associated with a Th1 response.