LIPOCORTIN-1 (ANNEXIN-1) SUPPRESSES ACTIVATION OF AUTOIMMUNE T-CELL LINES IN THE LEWIS RAT

Increased levels of lipocortins occur in the nervous system in multipl e sclerosis, in experimental autoimmune encephalomyelitis and experime ntal neuritis at the height of disease and decrease thereafter, sugges ting their potential involvement in recovery from disease. We therefor e investigated whether lipocortins may suppress activation of autoimmu ne. T cells. Antigen-specific and growth factor-mediated proliferation of T cell lines reactive with myelin basic protein (MBP) was measured in the presence of recombinant lipocortin-1, -2, and -5, and natural bovine lipocortin-1 using various concentrations and incubation period s. We also employed an N-terminal lipocortin-1 peptide spanning aa 1-2 6, a proteolytic fragment of lipocortin-1 where the respective N-termi nal region was clipped off, tested blocking with a neutralizing antibo dy, and investigated the effect of alkaline phosphatase treatment. Bot h human recombinant and bovine lipocortin-1 had a marked suppressive e ffect on T cell activation by MBP and the respective immunogenic pepti de. When added at 3 mu g/ml we observed up to 90% inhibition of T cell proliferation between day 2 and 3, but not at earlier time points of activation. The inhibitory effect of human lipocortin-1 was blocked af ter addition of a neutralizing antibody directed against lipocortin-1. Lipocortin-2 and -5, and the N-terminal peptide of lipocortin-1 were ineffective, whereas the fragment spanning residues 27-345 of lipocort in-1 retained full activity. Treatment of bovine lipocortin-1 with alk aline phosphatase did not alter immunosuppressive properties.