Alvarez et al.
Nov 3, 2008
This study explores the role of CD86 expression on human islet endothelial cells (ECs) in facilitating the adhesion and migration of T cells, particularly CD4+ T cells.
This study explores the role of CD86 expression on human islet endothelial cells (ECs) in facilitating the adhesion and migration of T cells, particularly CD4+ T cells. It demonstrates that CD86 on islet ECs plays a crucial role in T cell activation and transmigration across the endothelial barrier, which is important in autoimmune diseases like type 1 diabetes (T1D).
Key findings include:
Expression of Costimulatory Molecules: Human islet ECs constitutively express CD86 and ICOS-L but not CD80 or CD40. The presence of CD86 on islet ECs enables them to provide costimulatory signals to CD4+ T cells, promoting their activation and proliferation when co-cultured with anti-CD3-stimulated T cells.
Role in T Cell Adhesion: Blocking CD86 on islet ECs significantly inhibited the adhesion of CD4+ T cells, indicating that CD86 ligation plays a key role in this process.
T Cell Migration: Inhibition of CD86 also reduced the migration of CD4+ T cells across islet ECs, highlighting its importance in the recruitment of T cells into inflamed tissues, which is particularly relevant to the development of T1D.
CTLA-4 Interaction: CD86 on ECs interacts with CTLA-4 on T cells, facilitating adhesion and migration. The blockade of this interaction with CTLA-4Ig (abatacept) confirmed its critical role in T cell migration.
In conclusion, the study identifies CD86 as a key factor in the adhesion and migration of T cells across islet endothelial cells, contributing to the recruitment of autoreactive T cells in conditions like type 1 diabetes. This suggests that targeting CD86/CTLA-4 interactions may provide therapeutic benefits for autoimmune diseases by preventing T cell infiltration.