| First Author | Ndhlovu LC | Year | 2001 |
| Journal | J Immunol | Volume | 167 |
| Issue | 5 | Pages | 2991-9 |
| PubMed ID | 11509650 | Mgi Jnum | J:119463 |
| Mgi Id | MGI:3702244 | Doi | 10.4049/jimmunol.167.5.2991 |
| Citation | Ndhlovu LC, et al. (2001) Critical involvement of OX40 ligand signals in the T cell priming events during experimental autoimmune encephalomyelitis. J Immunol 167(5):2991-9 |
| abstractText | OX40 ligand (OX40L) expressed on APCs, and its receptor, OX40 present on activated T cells, are members of the TNF/TNFR family, respectively, and have been located at the sites of inflammatory conditions. We have observed in OX40L-deficient mice (OX40L(-/-)) an impaired APC capacity and in our recently constructed transgenic mice expressing OX40L (OX40L-Tg), a markedly enhanced T cell response to protein Ags. Using these mice, we demonstrate here the critical involvement of the OX40L-OX40 interaction during the T cell priming events in the occurrence of experimental autoimmune encephalomyelitis (EAE). In OX40L(-/-) mice, abortive T cell priming greatly reduced the clinical manifestations of actively induced EAE, coupled with a reduction in IFN-gamma, IL-2, and IL-6 production in vitro. Adoptive transfer experiments however revealed an efficient transfer of disease to OX40L(-/-) mice using wild-type donor T cells, indicating an intact capacity of OX40L(-/-) mice to initiate effector responses. On the other hand, OX40L(-/-) donor T cells failed to transfer disease to wild-type recipient mice. Furthermore, OX40L-Tg mice developed a greater severity of EAE despite a delayed onset, while both OX40L-Tg/CD28(-/-) and OX40L-Tg/CD40(-/-) mice failed to develop EAE demonstrating a requisite for these molecules. These findings indicate a pivotal role played by OX40L in the pathogenesis of EAE. |
