Expression of the H2-E molecule mediates protection to collagen-induced arthritis in HLA-DQ8 transgenic mice: role of cytokines

Abstract

Transgenic mice expressing DQA1*0301 and DQB1*0302 (HLA-DQ8) molecules in class II-deficient Ab degree 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 into DQ8.Ab degree mice to generate DQ8/E+.Ab degree mice. Expression of the E molecule protects DQ8.Ab degree mice against arthritis. In vitro studies using draining lymph nodes from mice primed with bovine type II collagen (BII) showed that the response to BII in both transgenics is DQ and CD4 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 hypothesized that the H2-E molecule modulates the T cell repertoire and changes the cytokine balance, resulting in protection of disease.