Gene expression profiling of allogeneic islet grafts in an experimental mouse model before rejection or tolerance phenotypes arise.

BACKGROUND

It has been reported that an HY antigen-mismatched islet transplantation can induce peripheral tolerance. However, the factors that initiate the peripheral tolerance are not clear. This study was designed to examine which genes were most important for the induction of peripheral tolerance.

METHODS

Islets from female Balb/c and male C57BL/6 mice were transplanted underneath the left perirenal capsule of female C57BL/6 recipient mice rendered diabetic by intraperitoneal injection of streptozotocin. Before rejection or tolerance phenotypes arose, we harvested islet grafts for cDNA microarray analysis.

RESULTS

Minor antigen-mismatched islets transplanted into recipient mice showed no rejection or tolerance phenotypes until 12 days posttransplantation. When we confirmed, decreased functional islet grafts and increased inflammatory cell infiltration. Gene expression profiles revealed differences in expression among groups. Major histocompatibility complex-mismatched islets induced upregulation of 209 genes and downregulation of 10 genes compared with the HY antigen-mismatched islet (2-fold; P < .05). Of these, 3 genes exhibited significant changes in expression levels in Balb/c donor islet grafts compared with C57BL/6 donor islet grafts: Gad1, Gdf10, and Scg2 (P < .01).

CONCLUSIONS

The present study suggested that 3 genes showed a significant relationship to protection against graft rejection. The identification of these genes may help to understand signaling pathways, involved in the communication between transplanted islet grafts and recipients in vivo.