Where CD4+CD25+ T reg cells impinge on autoimmune diabetes

Area of Science:

• Immunology
• Endocrinology
• Autoimmunity

Background:

• CD4(+)CD25(+) regulatory T (T reg) cells are crucial for controlling autoimmune diseases like type-1 diabetes.
• The precise location where T reg cells exert their suppressive function in the autoimmune cascade is not fully understood.

Purpose of the Study:

• To investigate the role of T reg cells in the diabetogenic cascade by examining their impact on effector T cell activation and pancreatic islet infiltration.
• To determine whether T reg cells primarily act in lymph nodes or within the pancreatic islets to prevent type-1 diabetes.

Main Methods:

• Utilized a Foxp3 scurfy mutation crossed with a BDC2.5 T cell receptor transgenic mouse model to eliminate T reg cells.
• Analyzed effector T cell activation and phenotype in draining lymph nodes.
• Assessed T cell infiltration of pancreatic islets (insulitis) and progression to diabetes.
• Performed microarray analysis to compare gene expression profiles of T reg cells in different locations.

Main Results:

• Absence of T reg cells did not alter initial effector T cell activation in lymph nodes or accelerate islet infiltration.
• However, insulitis in the absence of T reg cells was rapidly destructive, leading to overt diabetes.
• T reg cells within pancreatic islets exhibited a distinct gene expression program compared to those in lymph nodes.

Conclusions:

• T reg cells primarily control autoimmune diabetes by suppressing destructive T cells directly within the pancreatic islets.
• The suppressive function of T reg cells within the islets is more critical than their role during initial T cell activation in lymph nodes.