Details

Autor(en) / Beteiligte

• Duncan, Beverly
• Nazarov-Stoica, Cristina
• Surls, Jacqueline
• Kehl, Margaret
• Bona, Constantin
• Casares, Sofia
• Brumeanu, Teodor-D

Titel

Double Negative TCR[alpha][beta] Splenic Cells from Young NOD Mice Provide Long-Lasting Protection against Type 1 Diabetes

Ist Teil von

• PloS one, 2010-07, Vol.5 (7), p.e11427

Ort / Verlag

Public Library of Science

Erscheinungsjahr

2010

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Background Double negative CD3.sup.+ 4.sup.- 8.sup.- TCR[alpha][beta] splenic cells (DNCD3) can suppress the immune responses to allo and xenografts, infectious agents, tumors, and some autoimmune disorders. However, little is known about their role in autoimmune diabetes, a disease characterized by the reduction of insulin production subsequent to destruction of pancreatic [beta]-cells by a polyclonal population of self-reactive T-cells. Herein, we analyzed the function and phenotype of DNCD3 splenic cells in young NOD mice predisposed to several autoimmune disorders among which, the human-like autoimmune diabetes. Methodology/Principal Findings DNCD3 splenic cells from young NOD mice (1) provided long-lasting protection against diabetes transfer in NOD/Scid immunodeficient mice, (2) proliferated and differentiated in the spleen and pancreas of NOD/Scid mice and pre-diabetic NOD mice into IL-10-secreting T.sub.R -1 like cells in a Th2-like environment, and (3) their anti-diabetogenic phenotype is CD3.sup.+ (CD4.sup.- CD8.sup.- )CD28.sup.+ CD69.sup.+ CD25.sup.low Foxp3.sup.- iCTLA-4.sup.- TCR[alpha][beta].sup.+ with a predominant V[beta]13 gene usage. Conclusions/Significance These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4.sup.+ CD25.sup.high Foxp3.sup.+ T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes.