EXPRESSION OF THE H2-E MOLECULE MEDIATES PROTECTION TO COLLAGEN-INDUCED ARTHRITIS IN HLA-DQ8 TRANSGENIC MICE - ROLE OF CYTOKINES

Transgenic mice expressing DQA10301 and DQB1*0302 (HLA-DQ8) molecules in class Il-deficient Ab(o) mice are susceptible to collagen-induced arthritis (CIA), To evaluate the role of the H2-E molecule (a homolog of HLA-DR) in DQ-restricted arthritis, the H2-E gene was introduced in to DQ8.Ab(o) mice to generate DQ8/E+.Ab(o) mice. Expression of the E m olecule protects DQ8.Ab(o) mice against arthritis. In vitro studies us ing draining lymph nodes from mice primed with bovine type It collagen (BII) showed that the response to BII in both transgenics is DQ and C D4 restricted, Challenge with BII in vitro leads to production of high levels of IFN-gamma in DQ8 and IL-4 in DQ8/E+ mice, We have hypothesi zed that the H2-E molecule modulates the T cell repertoire and changes the cytokine balance, resulting in protection of disease.