alpha 4 Integrins and L-selectin Differently Orchestrate T-cell Activity During Diabetes Prevention Following Oral Administration of CTB-insulin

• Published in: Journal of autoimmunity 2002-12, Vol.19 (4), p.223-232
• Main Authors: Aspord, C, Czerkinsky, C, Durand, A, Stefanutti, A, Thivolet, C
• Format: Article
• Language: English
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.2002.0610

Oral administration of insulin conjugated to the B chain of cholera toxin (CTB-insulin) in non-obese diabetic (NOD) mice results in diabetes prevention. We investigated the respective contributions of L-selectin (CD62L) and alpha 4-integrin pathways during CTB-driven tolerance. Purified CD62L+CD4+ cells from CTB-insulin fed mice significantly reduced the capacity of diabetogenic T cells to transfer diabetes in syngeneic recipients. In vivo antibody blockade of fed animals during adoptive co-transfer experiments indicated that both CD62L and alpha 4-integrins pathways were necessary to develop a protective response after oral tolerance induction. In contrast, when antibodies were given to recipient mice, only CD62L was critical for the protection. In vitro stimulated CD62L+CD4+ cells from the spleen of fed animals secreted lower amounts of IL-4 and IL-10 but comparable levels of TGF beta than CD62L-cells. A reduced IFN- gamma production between the two cell subsets was specifically observed in CTB-insulin fed mice. Furthermore, antibody treatments induced changes in T-cell migration to the spleen, mesenteric and pancreatic lymph nodes. The protective effect was also associated with migration of regulatory T cells into pancreatic islets. Taken together, our results suggest that L-selectin and alpha 4-integrin have distinct but complementary roles in the generation and function of regulatory CD4+ T cells following CTB-insulin administration.Copyright 2002 Elsevier Science Ltd. All rights reserved.