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

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.1AR1 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.1AR1 background strain apparently contains regulatory potential, which is able to counteract the autoimmune response.

• Autoimmunity
• diabetes
• rodent
• T-lymphocytes
• type 1 diabetes mellitus
• animal model

Acknowledgements

We gratefully acknowledge the skilful technical assistance of M. Meyer and S. Eghtessadi. H.W. was a graduate student in the Graduate Research Training Programme No. 705 funded by the Deutsche Forschungsgemeinschaft. This work has been supported by a grant from the Deutsche Forschungsgemeinschaft to A.J. and by the NIH grant 1R21AI55464-01 to S.L. and H.J.H.