TARGETING OF PANCREATIC-ISLETS OF SEVERE COMBINED IMMUNODEFICIENT MICE BY PASSIVE TRANSFER OF ALLOGENEIC SPLEEN-CELLS FROM NONOBESE DIABETIC MICE

The precise role of immune cells in beta cell killing and their manner of invasion of pancreatic islets in insulin-dependent diabetes mellitus (IDDM) are unclear. We have attempted to target pancreatic islets of severe-combined immunodeficient (SCID) mice with spleen cells from diabetic and non-diabetic female non-obese diabetic (NOD) mice given i.p. or i.v. Pancreatic, liver and kidney sections of SCID mice were assessed histologically for the presence of donor cells. The presence of raised levels of serum Ig was also used as an index of engraftment of donor cells in the periphery of SCID mice. All six SCID mice which received i.v. spleen cells from normal Swiss mice died within 2 weeks from graft versus host disease (GVHD) whereas five out of nine mice survived for 30 days after i.p. injection. No deaths were recorded after i.v. or i.p. injection of spleen cells from NOD mice. Pancreatic islets of four out of six SCID recipients of diabetic and three out of five recipients of non-diabetic spleen cells following i.p. injection showed lymphocytic infiltrates in the peri-islet and perivascular regions. All SCID mice which received i.v. spleen cells from diabetic (six SCID recipients) and non-diabetic NOD mice (seven SCID recipients) showed peri-islet and perivascular infiltrates in their pancreas. Immunohistochemical analysis showed that the islet engrafted cells were of CD4 and CD8 phenotype. Donor cells were also observed in the exocrine pancreas of some recipients. A majority of mice showed various degrees of lymphocytic aggregates in the perivascular regions of the liver but not in the kidney. Two of the five mice which received i.p. cells from Swiss mice also showed some perivascular and peri-islet lymphocytes in the pancreas. Significant but variable levels of mouse Ig were detected in all SCID sera which received spleen cells. These results demonstrate that spleen cells when passively transferred from NOD mice engraft islets of SCID recipients and reconstitute the periphery. However, additional studies are required to improve the specificity of homing of diabetogenic lymphocytes into the islets of these immunodeficient mice.