Multiple low-dose streptozotocin-induced diabetes in the mouse: further evidence for involvement of an anti-B cell cytotoxic cellular auto-immune response

R. C. McEvoy, N. M. Thomas, C. Hellerström, F. Ginsberg-Fellner, T. M. Moran

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Anti-B cell auto-immunity may play a role in the pathogenesis of diabetes in mice resulting from multiple subdiabetogenic doses of the pancreatic B cell toxin, streptozotocin. In the present study we have investigated the cytotoxic anti-B cell response in these mice. A major role for B lymphocytes, macrophages, or their products in the cytotoxic response originally detected in vitro was eliminated by passing splenocytes from the mice treated with multiple subdiabetogenic doses of streptozotocin over a nylon wool column. The removal of the adherent cells enhanced the cytotoxicity against a rat insulinoma cell line in vitro by that expected due to enrichment of T-lymphocytes by approximately twofold. The induction of diabetes after multiple subdiabetogenic doses of streptozotocin is strain dependent. Mice of five strains were immunized with rat insulinoma cells, but only splenocytes from the two strains susceptible to multiple subdiabetogenic doses of streptozotocin demonstrated a significant cytotoxic response against the rat insulinoma cells in vitro. Mice pre-immunized with either the rat insulinoma cells or with syngeneic islets labelled in vitro with the hapten trinitrophenol developed hyperglycaemia more rapidly than control mice after multiple subdiabetogenic doses of streptozotocin. In the latter experiment the control mice immunized with complete Freund's adjuvant alone also became hyperglycaemic after a modified multiple subdiabetogenic dose of streptozotocin that did not cause diabetes in non-immunized mice. In mice pre-treated with either adjuvant or cyclophosphamide and then given a modified multiple subdiabetogenic dose of streptozotocin (35 mg/kg × 5 rather than 40 mg/ kg) the degree of hyperglycaemia was reduced and there was no protective effect of cyclophosphamide. However, the mice pre-treated with adjuvant again developed hyperglycaemia more rapidly and to a much higher level than did the mice given multiple subdiabetogenic doses of streptozotocin only. These additional data further support the hypothesis that B-cell destruction after multiple subdiabetogenic doses of streptozotocin results from triggering of an immune response against these insulin-producing cells.

Original languageEnglish
Pages (from-to)232-238
Number of pages7
JournalDiabetologia
Volume30
Issue number4
DOIs
StatePublished - Apr 1987

Keywords

  • Insulin-dependent diabetes
  • auto-immunity
  • cellular immunity
  • mouse
  • streptozotocin

Fingerprint

Dive into the research topics of 'Multiple low-dose streptozotocin-induced diabetes in the mouse: further evidence for involvement of an anti-B cell cytotoxic cellular auto-immune response'. Together they form a unique fingerprint.

Cite this