Diabetes 53:3115-3119, 2004 © 2004 by the American Diabetes Association, Inc. Absence of Lymph Nodes in NOD Mice Treated With Lymphotoxin-ß Receptor Immunoglobulin Protects From Diabetes
1 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
Pregnant nonobese diabetic (NOD) mice were treated with lymphotoxin-ß receptor immunoglobulin fusion protein (LTßR-Ig) or control human immunoglobulin on days embryonic day 11 (E11) and E14, and offspring were followed for the development of antiß-cell antibodies, islet pathology, and hyperglycemia. The development of antiß-cell surface antibodies was abrogated in treated mice compared with controls. Autopsy examination of the mice at 30 weeks of age revealed normal development of secondary lymphoid structures in the control animals; however, mice treated with LTßR-Ig had no axillary, inguinal, popliteal, or peripancreatic lymph nodes. Histological examination of the pancreata of the control mice revealed a severe and destructive mononuclear cellular infiltrate in the islets, whereas the islets of the LTßR-Igtreated mice were devoid of any insulitis. None of the LTßR-Igtreated mice (n = 22) developed diabetes; in contrast, 80% of the control mice (n = 46) developed diabetes at 1 year of age. The LTßR-Igtreated mice did not contain diabetogenic T-cells. However, the treated mice developed diabetes upon inoculation with diabetogenic T-cells. In this model of spontaneous autoimmune diabetes, secondary lymphoid structures, most likely the peripancreatic lymph nodes, were essential for the development of pathologic antiß-cell autoimmunity.
Address correspondencereprint requests to Emil R. Unanue, MD, Campus Box 8118, 660 S. Euclid Av., St. Louis, MO 63110. E-mail: unanue{at}pathology.wustl.edu
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