题名：Soluble factors secreted by T-cells promote beta-cell proliferation.
作者：DIRICE E; KAHRAMAN S; JIANG W; EL OUAAMARI A; DE JESUS DF; TEO AK; HU J; KAWAMORI D; GAGLIA JL; MATHIS D; KULKARNI RN;
来源：Diabetes. 2013 Oct 2. [ IF= 7.89 ] ]
摘要：Type 1 diabetes is characterized by infiltration of pancreatic islets with immune
cells leading to insulin deficiency. While infiltrating immune cells are
traditionally considered to negatively impact beta-cells by promoting their
death, their contribution to proliferation is not fully understood. Here we
report that islets exhibiting insulitis also manifested proliferation of
beta-cells which positively correlated with the extent of lymphocyte
infiltration. Adoptive transfer of diabetogenic CD4+ and CD8+ T-cells, but not
B-cells, selectively promoted beta-cell proliferation in vivo independent from
the effects of blood glucose, circulating insulin or by modulating apoptosis.
Complementary to our in vivo approach co-culture 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 cytokine/chemokines (IL-2, IL-6, IL-10,
MIP-1alpha and RANTES) that together enhanced beta-cell proliferation. These data
suggest that soluble factors secreted from T cells are potential therapeutic
candidates to enhance beta-cell proliferation in efforts to prevent and/or delay
the onset of type 1 diabetes.