of naive T cells in order to retain the developing effector cells in the lymphoid tissue as they undergo differentiation and clonal expansion (see Section 9-6). Most effector T cells also shed L-selectin, which mediates rolling on the high endothelial venules of secondary lymphoid tissues such as lymph nodes, in favor of P-selectin glycoprotein ligand-1 (PSGL-1), a homodimeric sialoglycoprotein that is the major ligand for tethering and rolling on the Pand E-selectin expressed by activated endothelial cells at sites of inflammation (Fig. 11.6). In contrast to granulocytes and monocytes, which constitutively express glycosyltransferases necessary for biosynthesis of selectin ligands, T cells express these enzymes only after effector T-cell development. Effector differentiation induces expression of the glycosyltransferase α1,3-fucosyltransferase VII (FucT-VII), a key enzyme required for both Pand E-selectin ligand generation. Thus, although PSGL-1 is expressed by both naive and effector T cells, it is appropriately glycosylated for selectin binding only by effector T cells.
The expression of other adhesion molecules such as integrins that are important for the recruitment of effector T cells to inflamed tissues is also increased (see Fig. 11.6). Naive T cells mainly express LFA-1 (αLβ2), which is retained on effector T cells as they develop from naive T-cell precursors. However, LFA-1 is not the only integrin that these cells express. Effector T cells also synthesize the integrin α4:β1, or VLA-4, which binds to the adhesion molecule VCAM-1, a member of the immunoglobulin superfamily related to ICAM-1. When T cells are activated by chemokine signaling, VLA-4 is altered so that it can bind to VCAM-1 with greater affinity, similar to chemokine-induced binding of activated LFA-1 to ICAM-1 (see Section 3-18). Thus, chemokines activate VCAM-1 to bind VLA-4 on vascular endothelial cells near sites of inflammation, allowing extravasation of effector T cells. Although both VCAM-1 and ICAM-1 are expressed on activated endothelial cell surfaces, there appears to be preferential utilization of one of the two adhesion pairs in some inflamed tissue vascular beds: recruitment of effector T cells is more dependent on VLA-4 in some tissues, and more dependent on LFA-1 in others.
Induction of expression of some adhesion molecules is compartmentalized so that effector T cells primed within lymphoid compartments of those tissues home back to them, whether during an active immune response or at homeostasis. Thus, the site of priming appears to imprint effector T cells with the ability to traffic to particular tissues. This is achieved by the expression of adhesion molecules that bind selectively to tissue-specific addressins. In this context, the adhesion molecules are often known as homing receptors (Fig. 11.7). As we shall see in Chapter 12, dendritic cells that prime T cells in the gut-associated lymphoid tissues (GALT) induce expression of the α4:β7 integrin, which binds to the mucosal vascular addressin MAdCAM-1 that is constitutively expressed by endothelial cells of blood vessels within the gut mucosa (see Fig. 11.7, lower left panel).
T cells primed in the GALT also express specific chemokine receptors that bind chemokines produced constitutively—and specifically—by the gut epithelium. Thus, at homeostasis CCR9 expressed on T cells primed in lymphoid