B7.2 has opposing roles during the activation versus effector stages of experimental autoimmune thyroiditis

APCs provide costimulatory and down-regulatory signals to Ag-activated T ce lls through interactions between B7.1 and B7.2 on APCs with either CD28 or CTL Ag-4 expressed on T cells. Recipients of mouse thyroglobulin (MTg)-prim ed spleen cells activated in the presence of anti-B7.2 had decreased experi mental autoimmune thyroiditis (EAT) severity compared with recipients of ce lls cultured with control rat Ig or anti-B7.1. Blocking B7.2 during in vivo priming also suppressed the ability of MTg-primed spleen cells to transfer EAT, implicating a role for B7.2 for priming and in vitro activation of EA T effector cells. In contrast, administration of anti-B7.2 or anti-B7.2 Fab to recipients of MTg-activated spleen cells increased the severity of EAT compared with recipients receiving control Ig, Thyroids from anti-B7.2-trea ted recipients had increased expression of IL-4 mRNA compared with thyroids from rat Ig-treated controls, Both B7.1 and B7.2 molecules were expressed in the thyroids of mice with EAT, although B7.2 was more prevalent than B7. 1. Administration of both anti-B7.1 and anti-B7.2 to recipient mice suppres sed the development of EAT, while anti-B7.1 treatment alone had no effect o n EAT severity. The suppression of EAT was not observed when anti-B7.1 and anti-B7.2 treatment was delayed until 7 days after cell transfer, suggestin g a requirement for B7 in the initiation of EAT in recipient mice. These re sults suggest that costimulation is required during the effector phase of E AT and that B7.2 may have opposing roles in the activation versus effector stages of autoreactive T cells.