PHENOTYPIC ANALYSIS OF RETINAL LEUKOCYTE INFILTRATION DURING COMBINEDCYCLOSPORINE-A AND NASAL ANTIGEN ADMINISTRATION OF RETINAL ANTIGENS -DELAY AND INHIBITION OF MACROPHAGE AND GRANULOCYTE INFILTRATION

Nasal antigen administration successfully suppresses a model of organ- specific autoimmune disease, experimental autoimmune uveoretinitis (EA U), when administered prior to immunisation. We have previously shown that nasal antigen therapy for active disease or in primed, sensitised animals does not reliably or consistently suppress histological disea se. However, when nasal antigen administration is combined with cyclos porin A (CsA) therapy, rod outer segment destruction (target organ) is reduced despite the presence of clinical and histological leukocytic infiltration of the eye. In this study, two colour flow cytometric phe notypic analysis of retinal and choroidal leukocytic infiltration of a nimals treated with either CsA alone, combined therapy with CsA and in halational tolerance therapy with retinal antigens or sham treated con trols was performed. There was no clinical difference between the two treated groups. Flow cytometric phenotypic analysis was performed in a ll groups at both maximal clinical disease and during resolution of cl inical signs. Although the cell number within the infiltrate was reduc ed in combined treated group, CD4+ IL-2R(+) T cells were still present in large numbers, in contrast to the markedly reduced numbers of ED7 (macrophages/granulocytes) cells infiltrating during height of diseas e. In the CsA-nasal antigen treated group, when clinical inflammation had subsided, an increase in both macrophages and granulocyte numbers in the chorioretina was observed. The cell numbers were always less th an CsA-only treated animals. Despite the late cellular influx of monoc ytes/macrophages, rod outer segment (ROS) integrity as determined hist ologically, was maintained. Nasal antigen administration of retinal an tigens in CsA-only treated animals (combined therapy group) protects a gainst target organ damage without inhibiting activated T cell traffic to the eye. These results suggest that recruitment of macrophages to the target tissue is central to autoimmune target organ damage, the me chanisms of which are discussed.