Double negative (CD3+ 4- 8-) TCR alphabeta splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes.
Double negative (CD3+ 4- 8-) TCR alphabeta splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes.
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DOI：
10.1371/journal.pone.0011427
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发表时间：
2010-07-02
期刊：
影响因子：
3.7
通讯作者：
Brumeanu TD
中科院分区：
文献类型：
--
作者：
Duncan B;Nazarov-Stoica C;Surls J;Kehl M;Bona C;Casares S;Brumeanu TD
双阴性CD 3 +4−8− TCRαβ脾细胞（DNCD 3）可以抑制对同种异体和异种移植物、感染因子、肿瘤和一些自身免疫性疾病的免疫反应。然而，关于它们在自身免疫性糖尿病中的作用知之甚少，该疾病的特征在于在自身反应性T细胞的多克隆群体破坏胰腺β细胞之后胰岛素产生减少。在此，我们分析了DNCD 3脾细胞的功能和表型的年轻NOD小鼠易患几种自身免疫性疾病，其中，类人自身免疫性糖尿病。来自年轻NOD小鼠的DNCD 3脾细胞（1）在NOD/Scid免疫缺陷小鼠中提供针对糖尿病转移的持久保护，（2）在Th 2样环境中在NOD/Scid小鼠和糖尿病前期NOD小鼠的脾和胰腺中增殖并分化为分泌IL-10的TR-1样细胞，（3）抗糖尿病表型为CD 3+（CD 4 − CD 8 −）CD 28 + CD 69 + CD 25 low Foxp 3 − iCTLA-4−TCRαβ+，主要使用Vβ13基因。这些发现描绘了一个新的T调节成分在自身免疫性糖尿病除了NKT和CD 4 + CD 25 highFoxp 3 + T调节细胞。DNCD 3脾细胞可能被操纵，以开发自身免疫性糖尿病的自体细胞疗法。
Double negative CD3+4−8− TCRαβ 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 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. 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 TR-1 like cells in a Th2-like environment, and (3) their anti-diabetogenic phenotype is CD3+(CD4−CD8−)CD28+CD69+CD25low Foxp3− iCTLA-4−TCRαβ+ with a predominant Vβ13 gene usage. These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4+CD25high Foxp3+T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes.
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影响因子：
30.5
作者：
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