The Role of CD8+ Cells, Cell Degeneration, and Fas Ligand in Insulitis After Intraperitoneal Transfer of NOD Splenocytes

Abstract

Cells expressing CD4, CD8, CD18, CD49d/CD29, CD44, CD54, CD80, CD86, CD106, CD11b/CD18 or DNA breaks were stained in the pancreases of female or male scid/ scid mice after adoptive transfer of lymphocytes from older than 12-week female nonobese diabetic (NOD) or Balb/c mice. After intraperitoneal adoptive transfer of NOD splenocytes to female severe combined immunodeficiency (scid)/scid mice, in situ end labeling (ISEL)+ as well as CD80+ and CD86+ cell infiltrates appeared first in the blood vessel walls and pancreatic interstitial tissue at 2-3 weeks after transfer. CD4+, CD8+, CD18+, CD44+, CD54+, and CD106+ cells then encircled and invaded some islets of the scid/scid mice 2 to 7 weeks after transfer. Cells expressing these surface components, except CD8, were present also in the Balb/c mice, but as individual cells, not as infiltrates. CD8+ cells were observed in the pancreases of all NOD splenocyte-injected scid mice at 2, 3, 4, 6, and 7 weeks after transfer, but in none of the Balb/c splenocyte-injected scid mice. Some scid/scid mice injected with NOD splenocytes also developed severe noninfectious diarrhea and cachexia 4 weeks after transfer. ISEL+ cells were observed in the pancreases of NOD splenocyte-injected female scid mice at all times after transfer, especially in the blood vessel walls and in the islets. Fas ligand was not present in Western blotting. It is proposed that apoptosis commonly occurs in islet-infiltrating lymphocytes and that in the scid/scid adoptive-transfer model, the first islet-infiltrating cells are destroyed by programmed cell death independent of Fas ligand. Further, CD8+ T lymphocytes inevitably play a central role in intraperitoneal adoptive transfer of insulitis.