Purpose: To determine the location of the CC chemokines macrophage inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein (MCP)-1, and regulated on activation of normal T-cell-expressed and secreted (RANTES) during disease progression in experimental autoimmune uveitis (EAU) and their relationship with the presence of the T helper cell (Th)1-type cytokine IFNgamma.
Methods: EAU was induced by immunization of Lewis rats with retinal extract. Consecutive cryostat sections were prepared from eyes at different stages of EAU, graded for severity of uveitis and stained by using antibodies to MCP-1, MIP-1alpha, and RANTES and to cell surface markers. Supernatants from superficial cervical lymph node cells were examined by ELISA for IFNgamma, IL-4, and IL-10.
Results: MIP-1alpha and IFNgamma were present most frequently and most extensively at peak disease but also were detectable in the choroid 8 days after immunization, before clinical disease onset. MCP-1 and RANTES were present at peak disease, but much less frequently. RANTES was occasionally found in the choroid before clinical disease. By days 19 to 21 after immunization, although infiltrating cells were present, there were only residual low levels of chemokine staining. MCP-1 and RANTES were detected on CD3-positive cells and on some ED1-positive cells, whereas MIP-1alpha was also associated with vessels and areas of exudate. Lymph node cells cultured from animals with peak disease had increased levels of IFNgamma and IL-10, but for IFNgamma this occurred only after stimulation in vitro with retinal extract.
Conclusions: Although MCP-1 and RANTES were associated predominantly with cells infiltrating the retina, MIP-1alpha was also associated with resident cells. All three are likely to exacerbate EAU-MIP-1alpha, to the greatest degree.