Soluble factors secreted by T cells promote β-cell proliferation
Ercument Dirice, Sevim Kahraman, Wenyu Jiang, Abdelfattah El Ouaamari, Dario F De Jesus, Adrian K K Teo, Jiang Hu, Dan Kawamori, Jason L Gaglia, Diane Mathis, Rohit N Kulkarni, Ercument Dirice, Sevim Kahraman, Wenyu Jiang, Abdelfattah El Ouaamari, Dario F De Jesus, Adrian K K Teo, Jiang Hu, Dan Kawamori, Jason L Gaglia, Diane Mathis, Rohit N Kulkarni
Abstract
Type 1 diabetes is characterized by infiltration of pancreatic islets with immune cells, leading to insulin deficiency. Although infiltrating immune cells are traditionally considered to negatively impact β-cells by promoting their death, their contribution to proliferation is not fully understood. Here we report that islets exhibiting insulitis also manifested proliferation of β-cells that positively correlated with the extent of lymphocyte infiltration. Adoptive transfer of diabetogenic CD4(+) and CD8(+) T cells, but not B cells, selectively promoted β-cell proliferation in vivo independent from the effects of blood glucose or circulating insulin or by modulating apoptosis. Complementary to our in vivo approach, coculture of diabetogenic CD4(+) and CD8(+) T cells with NOD.RAG1(-/-) islets in an in vitro transwell system led to a dose-dependent secretion of candidate cytokines/chemokines (interleukin-2 [IL-2], IL-6, IL-10, MIP-1α, and RANTES) that together enhanced β-cell proliferation. These data suggest that soluble factors secreted from T cells are potential therapeutic candidates to enhance β-cell proliferation in efforts to prevent and/or delay the onset of type 1 diabetes.
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References
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