| First Author | Shi FD | Year | 1999 |
| Journal | J Immunol | Volume | 162 |
| Issue | 10 | Pages | 5757-63 |
| PubMed ID | 10229808 | Mgi Jnum | J:120564 |
| Mgi Id | MGI:3706767 | Doi | 10.4049/jimmunol.162.10.5757 |
| Citation | Shi FD, et al. (1999) Mechanisms of nasal tolerance induction in experimental autoimmune myasthenia gravis: identification of regulatory cells. J Immunol 162(10):5757-63 |
| abstractText | Autoantigen administration via nasal mucosal tissue can induce systemic tolerance more effectively than oral administration in a number of experimental autoimmune diseases, including Ab-mediated experimental autoimmune myasthenia gravis, a murine model of myasthenia gravis. The mechanisms underlying nasal tolerance induction are not clear. In this study, we show that nasal administration of acetylcholine receptor (AChR) in C57BL/6 mice, before immunizations with AChR in adjuvant, results in delayed onset and reduced muscle weakness compared with control mice. The delayed onset and reduced muscle weakness were associated with decreased AChR-specific lymphocyte proliferation and decreased levels of anti-AChR Abs of the IgG2a and IgG2b isotypes in serum. The clinical and immunological changes in the AChR-pretreated C57BL/6 wild-type (wt) mice were comparable with those observed in AChR-pretreated CD8-/- mice, indicating that CD8+ T cells were not required for the generation of nasal tolerance. AChR-pretreated wt and CD8-/- mice showed augmented TGF-beta and reduced IFN-gamma responses, whereas levels of IL-4 were unaltered. Splenocytes from AChR-pretreated wt and CD8-/- mice, but not from CD4-/- mice, suppressed AChR-specific lymphocyte proliferation. This suppression could be blocked by Abs against TGF-beta. Thus, our results demonstrate that the suppression induced in the present model is independent of CD8+ T cells and suggest the involvement of Ag-specific CD4+ Th3 cells producing TGF-beta. |
