| First Author | Kobayashi S | Year | 1999 |
| Journal | J Immunol | Volume | 163 |
| Issue | 7 | Pages | 4013-9 |
| PubMed ID | 10491004 | Mgi Jnum | J:110828 |
| Mgi Id | MGI:3641370 | Doi | 10.4049/jimmunol.163.7.4013 |
| Citation | Kobayashi S, et al. (1999) Beta 2-microglobulin-deficient background ameliorates lethal phenotype of the TGF-beta 1 null mouse. J Immunol 163(7):4013-9 |
| abstractText | TGF-beta 1 null (TGF-beta1-/-) mice die at 3-4 wk of age and show an autoimmune inflammatory phenotype associated with enhanced expression of both class I and II MHC molecules. To determine the role of MHC class I Ags in the autoimmune manifestations and the inflammation observed in TGF-beta 1-/- mice, we generated TGF-beta 1-/- mice in the genetic background of beta 2-microglobulin deficiency (beta 2M-/-). TGF-beta 1-/-;beta 2M-/- mice had improved survival compared with TGF-beta 1-/- mice. Histopathological examination showed less severe inflammation, especially in the heart, where Mac-2 reactive macrophages were significantly decreased as compared with TGF-beta 1-/- mice. In vivo depletion of CD8+ T cells in TGF-beta 1-/- mice confirmed suppression of inflammation and reduction in the severity of the wasting syndrome. MHC class II mRNA expression in TGF-beta 1-/-;beta 2M-/- mice was also lower than that in TGF-beta 1-/- mice, suggesting reduced systemic inflammation. Autoimmune response as judged by serum Ab titers to ssDNA and 16/6 Id and by immune complex deposits in kidney was reduced in TGF-beta 1-/-;beta 2M-/- mice, when compared with that in TGF-beta 1-/- mice. Our data thus indicate that MHC class I molecules influence the development of the autoimmunity and the inflammation seen in TGF-beta 1-/- mice and CD8+ T cells may have a contribution to the inflammation in TGF-beta 1-/- mice. |
