CD2-FAS transgene increases t cell immune response and elevates amyloidosis in the kidney of aged CD-I mice

Academic Article


  • Fas is a cell surface receptor that mediates apoptosis. We have previously demonstrated that an age-related apoptosis defect and immune senescence were circumvented in CD2-fas transgenic (Tg) CD1 mice. In the present study, we further observed a four-fold increased response of immunoglobulin to the T cell-dependent antigen, TNP-KLH, in aged Tg mice compared to that in age-matched nontransgenic (Tg") control. However, the mortality rate of Tg mice was equivalent to Tg" mice. Furthermore, aged Tg mice had an elevated concentration of blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) in the serum compared to that in Tg' control (BUN: 30±8 vs 21±5 mg/dL; LDH: 1463±488 vs 1000±260 U/L). Examination of renal histology revealed that in 50% of the Tg mice that died before 20month'old (BUN: 48±17), there was deposition of amyloid in 100% of the glomerulus, causing a marked alteration of glomerular structure; whereas, only minimal deposition was observed in Tg' control. Congo red staining of kidney sections showed that the apple green birefringence appears in glomerular tuft and, in pan, in tubular interstitial space. The amyloid in Tg kidney was further identified to be amyloid A using immunohistochemistry staining, suggesting chronic inflammation plays an important role in its deposition. Taken together, our results indicate that renal amyloidosis is one of the major causes of death in aged Tg CD1 mice. Therefore, although CD2-fas transgene mice may correct immune senescence and result in higher immune response, the negative effect of this treatment could be an imbalanced metabolism of a family of acute-phase protein, serum amyloid A, that subsequently leads to amyloidosis in the kidney.
  • Author List

  • Hsu HC; Zhou T; Young PY; Martin F; Mountz JD
  • Volume

  • 10
  • Issue

  • 6