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.
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.
Wedekind
Dirk
D
Institute of Laboratory Animal Science, Hannover Medical School, D-30623 Hannover, Germany. wedekind.dirk@mh-hannover.de
Weiss
Heike
H
Jörns
Anne
A
Lenzen
Sigurd
S
Tiedge
Markus
M
Hedrich
Hans-Jürgen
HJ
D019264:Adoptive Transfer / Q000191:economics; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001786:Blood Glucose / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010179:Pancreas / Q000276:immunology* / Q000473:pathology; D011070:Poly I-C; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*
D001786:Blood Glucose; D003208:Concanavalin A; D011070:Poly I-C