Alpha E: Table I.

Integrin αEβ7 (CD103) has been an enigmatic and tantalizing molecule (1). The history of experiments on its functional significance is a record of promise and disappointment in equal measure. CD103 has been considered to have a role mainly or exclusively in the mucosal immune system, but this supposition now needs to be reappraised. The molecule is expressed at high levels by mucosal T cells, especially the CD8+ population in the epithelium of the gut, but is found on small subsets of T cells elsewhere. It is also present on mucosal mast cells and mucosal dendritic APCs. This eccentric pattern of expression has recently been extended to include splenic CD4+ CD25+ Treg cells, ∼30% of which are CD103+ (2). A plausible explanation for the expression profile is that the αE subunit is transcriptionally regulated by transforming growth factor (TGF)-β. In fact, no other stimulus has consistently been shown to induce expression. Thus, CD103 is found on T cells residing in tissue microenvironments where bioactive TGF-β is abundant. This is often the case in the vicinity of epithelia and in situations in which chronic inflammation is taking place. The particular association of CD103+ cells with epithelia is also explained by the fact that its principal ligand is E-cadherin, an epithelial homophilic adhesion molecule. The relationships between the integrins discussed here and their ligands are shown in Table I. Table I. Studies on CD103 function have, until now, met with mixed fortunes. Like other integrins, when ligated it provides costimulation for T cell proliferation and effector function. Importantly, the interaction between CD103 and E-cadherin will substitute for that between lymphocyte function–associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1 in CD8+-mediated CTL effector function (3). This could be especially significant for epithelial target cells, which often lack ICAM-1. It has been suggested that CD103 could function as a homing receptor encouraging T cells to extravasate to the gut. However, the balance of evidence more clearly favors a role in retention or microlocalization of T cells in the vicinity of epithelia rather than in mucosal-specific homing. In contrast, the sister integrin of CD103, α4β7, is known to play an important role in the homing of leukocytes to mucosal sites. Initial studies on the CD103−/− mouse were somewhat disappointing in that the only noticeable change was a modest reduction in the numbers of mucosal T cells and a T cell–dependent dermatitis of unknown etiology (4–6).