Effects of polyinosinic-polycytidylic acid and adoptive transfer of immune cells in the Lew.1AR1-iddm rat and in its coisogenic LEW.1AR1 background strain

Autoimmunity. 2005 Jun;38(4):265-75. doi: 10.1080/08916930500114321.

Abstract

The importance of the cellular immune system for the development of T1DM in the LEW.1AR1-iddm rat was investigated by use of polyinosinic-polycytidylic acid (Poly I:C) and by adoptive transfer of concanavalin A (Con A) activated lymphocytes from diabetic LEW.1AR1-iddm rats and the coisogenic LEW.AR1 background strain. Poly I:C treatment induced diabetes, characterized morphologically by a diffuse infiltration of the pancreas, in up to 20% of the animals of the coisogenic LEW.1AR1 background strain. It did not increase the diabetes incidence of 30% of the LEW.1AR1-iddm strain. In contrast Poly I:C treatment induced diabetes in up to 80% of the animals of the Mhc congenic LEW.1WR1 strain. Adoptive transfer of lymphocytes activated by the T-cell mitogen Con A from diabetic donors doubled the incidence of diabetes, characterized morphologically by a focal insulitis, in diabetes prone LEW.1AR1-iddm recipients. In contrast, animals of the LEW.1AR1 background strain did not develop diabetes after adoptive transfer. Moreover, adoptive transfer of Con A activated lymphocytes from LEW.1AR1 rats to LEW.1AR1-iddm rats with 30 or 60% diabetes incidence, significantly decreased the incidence of diabetes in LEW.1AR1-iddm rats with 60% diabetes incidence. The results show that autoreactive lymphocytes induce beta cell destruction in the LEW.1AR1-iddm rat, while the LEW.AR1 background strain apparently contains regulatory potential, which is able to counteract the autoimmune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer / economics
  • Animals
  • Apoptosis / immunology
  • Blood Glucose / immunology
  • Concanavalin A / pharmacology
  • Diabetes Mellitus, Experimental / immunology*
  • Diabetes Mellitus, Experimental / pathology
  • Disease Models, Animal
  • Female
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Lymphocyte Activation / immunology
  • Male
  • Pancreas / immunology*
  • Pancreas / pathology
  • Poly I-C
  • Rats
  • Rats, Inbred Lew
  • Rats, Nude
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes / immunology*

Substances

  • Blood Glucose
  • Concanavalin A
  • Poly I-C