Reversal of Spontaneous Autoimmune Insulitis in Nonobese Diabetic Mice by Soluble Lymphotoxin Receptor

doi:10.1084/jem.193.11.1327

Published online 4 June 2001.

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© The Rockefeller University Press, 0022-1007/2001/6/1327/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 11, June 4, 2001 1327-1332

Brief Definitive Report

Reversal of Spontaneous Autoimmune Insulitis in Nonobese Diabetic Mice by Soluble Lymphotoxin Receptor

Qiang Wu^a, Benoît Salomon^a,b, Min Chen^a, Yang Wang^a, Lisa M. Hoffman^a, Jeffrey A. Bluestone^a,b, and Yang-Xin Fu^a
^a Committee on Immunology and the Department of Pathology, University of Chicago, Chicago, Illinois 60637
^b Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637

Correspondence to: Yang-Xin Fu, Department of Pathology and Immunology, University of Chicago, 5841 S. Maryland, Rm. J541, MC3083, Chicago, IL 60637. Tel:773-702-0929 Fax:773-834-8940 E-mail:yfu{at}midway.uchicago.edu.

One striking feature of spontaneous autoimmune diabetes is theprototypic formation of lymphoid follicular structures withinthe pancreas. Lymphotoxin (LT) has been shown to play an importantrole in the formation of lymphoid follicles in the spleen. Toexplore the potential role of LT-mediated microenvironment inthe pathogenesis of insulin-dependent diabetes mellitus (IDDM),an LTß receptor–immunoglobulin fusion protein(LTßR–Ig) was administered to nonobese diabeticmice. Early treatment with LTßR–Ig preventedinsulitis and IDDM, suggesting that LT plays a critical rolein the insulitis development. LTßR–Ig treatmentat a late stage of the disease also dramatically reversed insulitisand prevented diabetes. Moreover, LTßR–Ig treatmentprevented the development of IDDM by diabetogenic T cells inan adoptive transfer model. Thus, LTßR–Ig candisassemble the well established lymphoid microenvironment inthe islets, which is required for the development and progressionof IDDM.

Key Words: adhesion molecule, autoimmune diabetes, insulitis, lymphotoxin,lymphotoxin ß receptor

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