First Author | Oliveira-dos-Santos AJ | Year | 1999 |
Journal | J Immunol | Volume | 162 |
Issue | 8 | Pages | 4490-5 |
PubMed ID | 10201986 | Mgi Jnum | J:112149 |
Mgi Id | MGI:3655588 | Doi | 10.4049/jimmunol.162.8.4490 |
Citation | Oliveira-dos-Santos AJ, et al. (1999) CD28 costimulation is crucial for the development of spontaneous autoimmune encephalomyelitis. J Immunol 162(8):4490-5 |
abstractText | Multiple sclerosis (MS) is a severe central nervous system disease. Experimental autoimmune encephalomyelitis (EAE) mimics MS in mice. We report that spontaneous development of EAE in RAG-1-deficient mice transgenic for a myelin basic protein (MBP)-specific TCR (TgMBP+/RAG-1-/-) requires expression of the T cell costimulatory molecule CD28. Surprisingly, T cells from CD28-/-TgMBP+/RAG-1-/- mice proliferate and produce IL-2 in response to MBP1-17 peptide in vitro, excluding clonal anergy as the mechanism of CD28-regulated pathogenesis. Proliferation of autoaggressive T cells was dependent on the concentration of the MBP peptide, as was the development of MBP-induced EAE in CD28-deficient PL/J mice. These results provide the first genetic evidence that CD28 costimulation is crucial for MBP-specific T cell activation in vivo and the initiation of spontaneous EAE. |