| First Author | Ujiie H | Year | 2012 |
| Journal | Clin Immunol | Volume | 142 |
| Issue | 2 | Pages | 167-75 |
| PubMed ID | 22044750 | Mgi Jnum | J:180413 |
| Mgi Id | MGI:5306216 | Doi | 10.1016/j.clim.2011.10.002 |
| Citation | Ujiie H, et al. (2012) Noncollagenous 16A domain of type XVII collagen-reactive CD4(+) T cells play a pivotal role in the development of active disease in experimental bullous pemphigoid model. Clin Immunol 142(2):167-75 |
| abstractText | Bullous pemphigoid (BP), the most common autoimmune blistering disease, is caused by autoantibodies against type XVII collagen (COL17). We recently demonstrated that CD4(+) T cells were crucial for the production of anti-COL17 IgG and for the development of the BP phenotype by using a novel active BP mouse model by adoptively transferring immunized splenocytes into immunodeficient COL17-humanized mice. Noncollagenous 16A (NC16A) domain of COL17 is considered to contain the main pathogenic epitopes of BP, however, the pathogenicity of COL17 NC16A-reactive CD4(+) T cells has never been elucidated. To address this issue, we modulated the immune responses against COL17 in active BP model by using anti-CD40 ligand (CD40L) monoclonal antibody MR1, an inhibitor of the CD40-CD40L interaction, in various ways. First, we show the essential role of CD4(+) T cells in the model by showing that CD4(+) T cells isolated from wild-type mice immunized with human COL17 enabled naive B cells to produce anti-COL17 NC16A IgG in vivo. Second, we show that the activation of anti-COL17 NC16A IgG-producing B cells via CD40-CD40L interaction was completed within 5days after the adoptive transfer of immunized splenocytes. Notably, a single administration of MR1 at day 0 was enough to inhibit the production of anti-COL17 NC16A IgG and to diminish skin lesions despite the presence of restored anti-COL17 IgG at the later stage. In contrast, the delayed administration of MR1 failed to inhibit the production of anti-COL17 NC16A IgG and the development of the BP phenotype. These results strongly suggest that COL17 NC16A-reactive CD4(+) T cells play a pivotal role in the production of pathogenic autoantibodies and in the development of active disease in experimental BP model. |
