LEAPS peptide vaccination alters T cell phenotype and suppresses joint inflammation in a murine model of rheumatoid arthitis (P5223)

Abstract

Abstract Introduction. A major therapeutic goal in autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is to suppress responses against (auto)antigens present in the target organs. Antigen-specific therapies such as the Ligand Epitope Antigen Presentation System (LEAPS) technology offer such a possibility. Materials and Methods. We evaluated LEAPS therapy in the cartilage proteoglycan (PG) induced arthritis (PGIA) model of RA. After the onset of PGIA, mice were divided in 3 groups, each with a similar mean arthritis index (AI). One group was vaccinated with adjuvant only, and the other groups with one of two LEAPS conjugates of a PG epitope 70 (J-PG70 or derG-PG70) in adjuvant. The same vaccination was repeated two weeks later. AI was measured by visual scoring every other day for 5 weeks. Upon euthanization, the proportions of Th1, Th2, Th17, and regulatory T cells (Tregs) in the spleen were determined by flow cytometry, and PG-specific lymphocyte proliferation by [3H]thymidine uptake. Results. Disease severity (AI) was dramatically suppressed in mice vaccinated with the LEAPS conjugate derG-PG70 as compared with controls or animals receiving J-PG70 vaccine. Protection was associated with reduced PG-specific lymphocyte proliferation, decreased proportions of Th1/Th17 cells, and increases in Th2 cells and Tregs. Conclusion. The derG-PG70 vaccine is therapeutically effective in PGIA (a Th1 dominated disease) by inducing immune deviation in favor of Th2 and Treg cells.