The pathogenicity of islet-infiltrating lymphocytes in the non-obese diabetic (NOD) mouse.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

The pathogenicity of islet-infiltrating lymphocytes in the non-obese diabetic (NOD) mouse.

Clin Exp Immunol. 1999 Feb;115(2):260-7. Unique Identifier : AIDSLINE MED/99132256
Ablamunits V; Elias D; Cohen IR; Department of Immunology, the Weizmann Institute of Science,; Rehovot, Israel.

Abstract: The aim of the present study was to investigate the pathogenic properties of islet-infiltrating lymphocytes related to the severity of the autoimmune destruction of islet beta-cells in the NOD mouse. We analysed the development of insulin-dependent diabetes mellitus (IDDM) produced by adoptive transfer of islet lymphocytes from NOD into NOD.scid mice. Here we show that the transfer was most effective when both CD4+ and CD8+ T cells were present in the infiltrate, but CD4+ T cells alone were sufficient to cause the disease. Islet lymphocytes from both females and males transferred diabetes effectively, but the severity of IDDM was higher when female islet lymphocytes were used. Unexpectedly, the sensitivity of male islets to beta-cell damage was greater than that of female islets. Treatment of NOD females with a peptide of heat shock protein (hsp)60, p277, known to protect NOD mice from IDDM, reduced the pathogenicity of the islet lymphocytes. In contrast, administration of cyclophosphamide to males, a treatment that accelerates the disease, rendered the islet lymphocytes more pathogenic. More severe disease in the recipient NOD.scid mice was associated with more interferon-gamma (IFN-gamma)-secreting islet T cells of the NOD donor. The disease induced by islet lymphocytes was strongly inhibited by co-transfer of spleen cells from prediabetic mice, emphasizing the regulatory role of peripheral lymphocytes. Thus, the cellular characteristics of the islet infiltrate and the pathogenicity of the cells are subject to complex regulation.

Keywords: JOURNAL ARTICLE Adoptive Transfer Animal Cell Movement Cyclophosphamide CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Diabetes Mellitus, Insulin-Dependent/*IMMUNOLOGY Female Heat-Shock Proteins/PHARMACOLOGY Insulin/ISOLATION & PURIF Islets of Langerhans/CHEMISTRY/*IMMUNOLOGY/PATHOLOGY Male Mice Mice, Inbred NOD Mice, SCID Peptide Fragments/PHARMACOLOGY Sex Characteristics Spleen/CYTOLOGY/IMMUNOLOGY Support, Non-U.S. Gov't T-Lymphocytes/DRUG EFFECTS/*IMMUNOLOGY/TRANSPLANTATION
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A9950894

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