Th1 Cells Rolling on Selectins Trigger DAP12-Dependent Signals That Activate Integrin αLβ2

Area of Science:

• Immunology
• Cellular Biology
• Inflammation Research

Background:

• Neutrophils and effector T cells use selectins for rolling and integrins for arrest in postcapillary venules during inflammation.
• Chemokines signal to convert integrin αLβ2 to a high-affinity conformation for ICAM-1 interaction and arrest.
• Selectins in neutrophils trigger signaling for integrin αLβ2 intermediate-affinity conformation, slowing rolling, but this is unknown in T cells.

Purpose of the Study:

• To investigate whether selectins induce similar signaling events in T cells as they do in neutrophils.
• To elucidate the signaling pathways involved in T cell recruitment and migration to inflammatory sites.
• To identify novel molecules involved in T cell adhesion and trafficking.

Main Methods:

• In vitro studies using mouse Th1 cells rolling on P- or E-selectin.
• In vivo experiments to assess T cell migration into Ag-challenged tissues.
• Analysis of signaling pathways, including the role of ITAMs, TCR, integrin αLβ2, ICAM-1, and DAP12.

Main Results:

• Mouse Th1 cells rolling on selectins triggered signals for αLβ2-dependent slow rolling on ICAM-1.
• Selectin signaling in Th1 cells unexpectedly utilized DAP12, an ITAM-bearing protein not previously known to be expressed in these cells.
• Outside-in signaling through ligand-occupied αLβ2 also required DAP12.
• Cooperative selectin and chemokine signaling promoted αLβ2-dependent slow rolling, arrest, and migration into Ag-challenged tissues.

Conclusions:

• This study reveals a novel function for DAP12 in Th1 cells.
• A new mechanism for effector T cell recruitment to inflammation sites involving DAP12 and selectin signaling is described.
• Findings enhance understanding of T cell trafficking and immune responses in inflammatory conditions.