The Journal of Experimental Medicine
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Published online 29 July 2002 doi:10.1084/jem.20011353
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© Rockefeller University Press, 0022-1007/2002/8/369/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 3, August 5, 2002 369-377

Pancreatic Lymph Nodes Are Required for Priming of ß Cell Reactive T Cells in NOD Mice

Marie-Claude Gagnerault1,2, Jian Jian Luan1, Chantal Lotton2 and Françoise Lepault1,2

1 Centre National de la Recherche Scientifique Unité Mixte de Recherche 8603, Université René Descartes, Hôpital Necker, 75015 Paris, France
2 Institut National de la Santé et de la Recherche Médicale U561, Hôpital Saint Vincent de Paul, 75014 Paris, France

Address correspondence to Dr. Françoise Lepault, INSERM U561, Hôpital Saint Vincent de Paul, 82 Avenue Denfert Rochereau, 75014 Paris, France. Phone: 33-1-40-48-82-49; Fax: 33-1-40-48-83-52; E-mail: lepault{at}cochin.inserm.fr

Nonobese diabetic (NOD) mice develop spontaneous autoimmune diabetes that results from the destruction of insulin secreting ß cells by diabetogenic T cells. The time and location of the encounter of autoantigen(s) by naive autoreactive T cells in normal NOD mice are still elusive. To address these issues, we analyzed diabetes development in mice whose spleen or pancreatic lymph nodes (panLNs) had been removed. Excision of panLNs (panLNx) at 3 wk protected mice against insulin autoantibodies (IAAs), insulitis, and diabetes development almost completely, but had no effect when performed at 10 wk. The protection afforded by panLNx at weaning was not due to modifications of the immune system, the absence of autoreactive T cells, or the increase in the potency of regulatory T cells. That panLNs are dispensable during adult life was confirmed by the capacity of 10-wk-old panLNx irradiated recipients to develop diabetes upon transfer of diabetogenic T cells. In contrast, splenectomy had no effect at any age. Partial excision of mesenteric LN at 3 wk did not prevent accelerated diabetes by cyclophosphamide as panLNx did. Thus, in normal NOD mice, autoreactive T cell initial priming occurs in LNs draining the target organ of the disease from 3 wk of age.

Key Words: insulin-dependent diabetes mellitus • lymph node excision • splenectomy • T cell activation • autoimmunity


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