Pancreatic lymph nodes are required for priming of beta cell reactive T cells in NOD mice.
Nonobese diabetic (NOD) mice develop spontaneous autoimmune diabetes that results from the destruction of insulin secreting beta 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.
Gagnerault
Marie-Claude
MC
Centre National de la Recherche Scientifique Unité Mixte de Recherche 8603, Université René Descartes, Hôpital Necker, 75015 Paris, France.
Luan
Jian Jian
JJ
Lotton
Chantal
C
Lepault
Françoise
F
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D002465:Cell Movement; D003520:Cyclophosphamide / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000502:physiology*; D013156:Splenectomy; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D007328:Insulin; D003520:Cyclophosphamide