T-cell migration to vascularized organ allografts

Abstract

Purpose of review: To review the classical paradigm of leukocyte migration and present new evidence that cognate antigen, and not signaling via Gαi-coupled chemokine receptors, drives the migration of effector and memory T cells into vascularized organ transplants.

Recent findings: Blocking Gαi function does not hinder integrin-dependent T-cell migration to heart and kidney allografts or significantly delay acute rejection. T-cell firm adhesion and transmigration is instead mediated by engagement of the T cell receptor for antigen (TCR) on antigen-specific (antidonor) T cells by cognate antigen presented by either graft endothelial cells or bone marrow-derived antigen-presenting cells that reach into the vascular lumen. Influx of bystander T cells is Gαi-dependent but occurs only if antigen-specific T cells are present.

Summary: Antigen-driven migration of effector and memory T cells sheds new light on the pathogenesis of transplant rejection and predicts that interrupting the TCR-triggered 'inside-out' signaling pathway, rather than that initiated by Gαi-coupled chemokine receptors, is a key approach to preventing rejection.