Details

Autor(en) / Beteiligte

• Kobayashi, S
• Yoshida, K
• Ward, J M
• Letterio, J J
• Longenecker, G
• Yaswen, L
• Mittleman, B
• Mozes, E
• Roberts, A B
• Karlsson, S
• Kulkarni, A B

Titel

Beta 2-microglobulin-deficient background ameliorates lethal phenotype of the TGF-beta 1 null mouse

Ist Teil von

• The Journal of immunology (1950), 1999-10, Vol.163 (7), p.4013-4019

Ort / Verlag

United States

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.