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Double negative (CD348) TCRαβ splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes

PLoS ONE, ISSN: 1932-6203, Vol: 5, Issue: 7, Page: e11427
2010
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Article Description

Background: Double negative CD34 TCRαβ splenic cells (DNCD3) can suppress the immune responses to alio 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 β-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-1 like cells in a Th2-like environment, and (3) their anti-diabetogenic phenotype is CD3(CD4CD8)CD28CD69CD25 Foxp3 iCTLA-4TCRαβ with a predominant Vβ13 gene usage. Conclusions/Significance: These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4+CD25 Foxp3T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes. © 2010 Nia et al.

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http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77955354249&origin=inward; http://dx.doi.org/10.1371/journal.pone.0011427; http://www.ncbi.nlm.nih.gov/pubmed/20625402; https://dx.plos.org/10.1371/journal.pone.0011427.g006; http://dx.doi.org/10.1371/journal.pone.0011427.g006; https://dx.plos.org/10.1371/journal.pone.0011427; https://dx.plos.org/10.1371/journal.pone.0011427.g001; http://dx.doi.org/10.1371/journal.pone.0011427.g001; https://dx.plos.org/10.1371/journal.pone.0011427.g005; http://dx.doi.org/10.1371/journal.pone.0011427.g005; https://dx.plos.org/10.1371/journal.pone.0011427.g004; http://dx.doi.org/10.1371/journal.pone.0011427.g004; https://dx.plos.org/10.1371/journal.pone.0011427.g003; http://dx.doi.org/10.1371/journal.pone.0011427.g003; https://dx.plos.org/10.1371/journal.pone.0011427.g002; http://dx.doi.org/10.1371/journal.pone.0011427.g002; https://dx.plos.org/10.1371/journal.pone.0011427.t001; http://dx.doi.org/10.1371/journal.pone.0011427.t001; https://dx.doi.org/10.1371/journal.pone.0011427.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0011427.g003; https://dx.doi.org/10.1371/journal.pone.0011427.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0011427.g001; https://dx.doi.org/10.1371/journal.pone.0011427; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011427; https://dx.doi.org/10.1371/journal.pone.0011427.g005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0011427.g005; https://dx.doi.org/10.1371/journal.pone.0011427.g004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0011427.g004; https://dx.doi.org/10.1371/journal.pone.0011427.t001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0011427.t001; https://dx.doi.org/10.1371/journal.pone.0011427.g006; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0011427.g006; https://dx.doi.org/10.1371/journal.pone.0011427.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0011427.g002; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0011427&type=printable; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0011427; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0011427&type=printable; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011427; http://dx.plos.org/10.1371/journal.pone.0011427.g005; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0011427; http://dx.plos.org/10.1371/journal.pone.0011427; http://dx.plos.org/10.1371/journal.pone.0011427.t001; http://dx.plos.org/10.1371/journal.pone.0011427.g004; http://dx.plos.org/10.1371/journal.pone.0011427.g003; http://dx.plos.org/10.1371/journal.pone.0011427.g006; http://dx.plos.org/10.1371/journal.pone.0011427.g002; http://dx.plos.org/10.1371/journal.pone.0011427.g001

Beverly Duncan; Cristina Nazarov–Stoica; Jacqueline Surls; Margaret Kehl; Constantin Bona; Sofia Casares; Teodor-D. Brumeanu; Derya Unutmaz

Public Library of Science (PLoS)

Multidisciplinary

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