T Cell Interactions with the Arterial Wall
T cells are found within the arterial wall in a number of pathological processes such as atherosclerosis, inflammatory aneurysms, certain forms of vasculitis, and in certain forms of acute and chronic vascular allograft rejection, namely intimal arteritis and allograft vasculopathy, respectively. We have used human cell culture and artery segments interpositioned into the abdominal aortae of immunodeficient mice to study the interactions of human T cells with allogeneic vascular cells and intact blood vessels. T cells of the effector memory subset can directly recognize non-self major histocompatibility complex molecules displayed by allogeneic endothelial cells (ECs), resulting in T cell trans-endothelial migration and activation. The survival of alloantigen-activated T cells is supported by NO release from chemokine-recruited T cells. In contrast to these interactions of T cells with ECs, vascular smooth muscle cells (VSMCs) inhibit T cell activation, largely through consumption of tryptophan by interferon (IFN)-³-induced indolamine 2,3-dioxygenase, converting the tunica media into a site of immune privilege. T cells do influence VSMC behaviors, e.g. by causing proliferation through the release of IFN-³. Signals that can increase the production of IFN-³, such as IL-1±, are released by injured or “activated” ECs, exacerbating these effect on VSMCs. This network of interactions may underlie key features of allograft vasculopathy, namely a subendothelial T cell infiltrate, an expanded intima composed of VSMCs, and a general sparing of the media.
- © 2010 by American Heart Association, Inc.