Class II MHC antigens in vivo induced by the diabetogen streptozotocin in BALB/c mice

Immunologic reactions are involved in the pathogenic pathway of hyperglycemia development induced by multiple subdiabetogenic doses of streptozotocin (STZ) in mice. Recently, we have reported that STZ, a nitro-surea derivative, can act in vivo as hapten for T lymphocytes, as assayed by applying the popliteal lymph node assay [1]. In subsequent experiments, induction of Class II major histocompatibility (MHC) antigens by STZ were evaluated in BALB/c mice. After subcutaneous injection of STZ a remarkable increment of Class II-positive cells was visible in multiple organs. Ia antigens were detected by a peroxidase method on cryo-cut sections using a monoclonal antibody with specificity for I−A d. A monoclonal antibody with specificity for Ia k was used as control. Definite increases of I−A d-binding cells were found in pancreatic, liver, kidney and heart tissue, but brain tissue remained unaffected. These Class II MHC alterations occurred on interstitial cells of the monocyte lineage, renal tubular cells and lymphoid cell infiltrates of the endocrine pancreas, but not on beta cells. Intense Ia-positivity at the pancreatic islet pole and at intra-insular sites was not necessarily associated with hyperglycemia development.