Primary herpes simplex virus type 1 infection of the eye triggers similar immune responses in the cornea and the skin of the eyelids.

Herpetic stromal keratitis (HSK) and blepharoconjunctivitis in humans are thought partly to result from immunopathological responses to herpes simplex virus type 1 (HSV-1). The corneas of NIH mice were inoculated with HSV-1 (strain McKrae) and mice were examined for signs of disease and infection on days 1, 4, 7, 10, 14 and 21. The eyes and eyelids of infected and control mice were processed for immunohistochemistry and double stained for viral antigens and one of the following cell surface markers (Gr-1, F4/80, CD4, CD8, CD45R or MHC class II) or one of the following cytokines (IL-2, IL-4, IL-6, IL-10, IL-12 or IFN-gamma). All infected mice developed signs of HSK by day 4 and blepharitis by day 7 and these both persisted until day 21, when signs of resolution where apparent. Virus was detected during the first week of infection and became undetectable by day 10. Large numbers of Gr-1(+) cells (neutrophils) infiltrated infected corneas and eyelids in areas of viral antigen and CD4(+) T cells increased significantly in number after virus clearance. In both sites, the predominant cytokines were IL-6, IL-10, IL-12 and IFN-gamma, with few IL-2(+) and IL-4(+) cells. These observations suggest that the immune responses in the cornea are similar to those in the eyelids but, overall, the responses are not clearly characterized as either Th1 or Th2. In both sites, the neutrophil is the predominant infiltrating cell type and is a likely source of the cytokines observed and a major effector of the disease process.

Regulation of mucosal immune responses by recombinant interleukin 10 produced by intestinal epithelial cells in mice.

BACKGROUND & AIMS: Interleukin (IL)-10 is a cytokine with anti-inflammatory properties. The aim of this study was to explore the effect of a site-specific delivery of IL-10 on intestinal immune responses. METHODS: Transgenic mice were created in which IL-10 is expressed by the intestinal epithelial cells. RESULTS: Transgenic mice showed a marked increase in the number of intraepithelial lymphocytes in the small intestine. Mucosal lymphocytes of transgenic animals produced fewer T helper type 1 cytokines than wild-type lymphocytes. By contrast, the production of transforming growth factor beta was increased. Moreover, the epithelial layer in transgenic mice was significantly enriched for CD4(+)CD25(+) T cells. Furthermore, transgenic mice had increased numbers of immunoglobulin A-producing B cells in the small intestine. These effects were local because splenic lymphocytes were not affected. Studies in models of inflammatory bowel disease showed that transgenic IL-10 was able to attenuate the acute colitis induced by dextran sodium sulfate administration or by adoptive transfer of CD4(+)CD45RB(high) splenocytes, with a modest effect on the chronic intestinal inflammation arising spontaneously in IL-10(-/-) mice. CONCLUSIONS: These observations provide evidence for an in vivo lymphoepithelial cross talk, by which cytokines locally produced by epithelial cells can regulate immune responses in the intestine without systemic modifications.