CD80(B7.1) and CD86(B7.2) do not have distinct roles in setting the Th1/Th2 balance in autoimmunity in rats.

Some data suggest that the interaction between CD28 and CD80 (B7.1) stimulates Th1-responses and that CD28 and CD86 (B7.2) stimulates Th2-responses, however this is controversial. We addressed this issue by using mercuric chloride (HgCl2)-induced autoimmunity in Brown Norway (BN) rats as a highly polarized Th2 model and experimental autoimmune encephalomyelitis (EAE) in Lewis rats as a highly polarized Th1 model. Monoclonal antibodies (MoAbs) to CD80 and CD86, given singly, had little effect in either model, however when given together they almost completely suppressed the HgCl2-induced autoimmunity: the peak immunoglobulin (Ig)E concentration was 3.25 microg/ml in treated animals versus 2770 microg/ml in controls (P < 0.0001); caecal vasculitis was suppressed with a median vasculitis score of 0 in treated animals versus 6 in controls (P < 0.0001); and new germinal centre formation was significantly suppressed. A combination of the antibodies also markedly reduced the severity of clinical EAE; from a median aggregate clinical score of 9 to 3 (P = 0.02) and delayed the onset from a median of 12.5 days to 16 days after immunization (P = 0.006). We have demonstrated profound suppression of both Th1 and Th2-driven autoimmunity in rats by a combination of anti-CD80 and CD86, but have been unable to demonstrate any clear differential effects.