Double Negative
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 reduct...
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Published in | PloS one Vol. 5; no. 7; p. e11427 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Public Library of Science
02.07.2010
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Subjects | |
Online Access | Get full text |
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Summary: | 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. 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. 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. |
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ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0011427 |