Constitutive expression of a costimulatory ligand on antigen-presenting cells in the nervous system drives demyelinating disease

SPECIFIC AIMSTo determine the role of organ-restricted antigen presentation in driving autoimmune diseases, we studied transgenic mice that constitutively express the costimulatory ligand B7.2 on resident antigen-presenting cells of the nervous tissue.PRINCIPAL FINDINGS1. B7.2 is constitutively expressed in the nervous tissue of B7.2 transgenic line 31 miceTo study the functional consequences of expression of a costimulatory ligand in a target organ of autoimmune disease, we used B7.2 transgenic mouse lines 27 and 31. Immunohistochemical studies and flow cytometric analyses of line 31 mice lacking mature α/β T cells (TCRβ −/− mice) or deficient in CD28 expression (CD28−/− mice) revealed elevated expression of B7.2 on microglia and spinal root macrophages (Fig. 1⤻ B). Levels of B7.2 expression on microglial cells in line 31 mice that contained T cells were equivalent (Fig. 1A⤻ ). B7.2 expression on microglia in line 27 mice was similar to that in wild-type animals (Fig. 1B⤻ ). B7.2 is therefore constitutiv...