When naive T cells differentiate into effector T cells, changes occur in the expression of specific surface molecules that redirect their trafficking from T-cell zones into B-cell zones, in the case of TFH cells, or from lymphoid to nonlymphoid tissues, in the case of other effector T cells. During the 3–5 days required for differentiation of naive T cells into effector T cells within secondary lymphoid tissues, marked changes occur in the expression of these trafficking molecules, including alterations in the display of selectins and their ligands, integrins, and chemokine receptors. As we will see, some of these changes are generic, and are common to all CD4 and CD8 effector T cells. Others are tissue-specific, facilitating the recruitment of T cells back to the tissues in which they were primed. Yet others are T-cell subset-specific, particularly the patterns of chemokine receptor expression, which are important in directing TFH cells to germinal centers, where they provide help to developing B cells, or in directing TH1, TH2, and TH17 cells to the same tissue sites as the myelomonocytic cells whose effector functions they will recruit and enhance.
Naive CD4 T cells that are activated by antigen and become TFH cells acquire expression of CXCR5 and lose expression of CCR7 and S1PR1, the receptor for the chemotactic lipid sphingosine 1-phosphate (see Section 9-7). The constitutive expression of CXCL13 by follicular dendritic cells establishes a gradient that attracts developing TFH cells first to the border of the T-cell zone with a B-cell follicle, where they can interact with B cells that present their cognate antigen, and then into the B-cell follicle, where they provide help to germinal center B cells. Unlike TFH cells, other effector CD4 and CD8 T cells must leave the lymphoid tissue in which they have developed to interact with myelomonocytic cells at sites of infection in nonlymphoid tissues. The exit of effector T cells is induced by their loss of CCR7 and their reexpression of S1PR1. S1PR1 is normally rapidly downregulated by CD69 following antigenic stimulation
Fig. 11.6 Effector T cells change their surface molecules, allowing them to home to sites of infection. Naive T cells home to lymph nodes through the binding of L-selectin to sulfated carbohydrates displayed by various proteins, such as CD34 and GlyCAM-1 (not shown), on the high endothelial venule (HEV, upper panel). After encounter with antigen, many of the differentiated effector T cells lose expression of L-selectin, leave the lymph node about 4–5 days later, and now express the integrin VLA-4 and increased levels of LFA-1 (not shown). These bind to VCAM-1 and ICAM-1, respectively, on peripheral vascular endothelium at sites of inflammation (lower panel). On differentiating into effector cells, T cells also alter their splicing of the mRNA encoding the cell-surface protein CD45. The CD45RO isoform expressed by effector T cells lacks one or more exons that encode extracellular domains present in the CD45RA isoform expressed by naive T cells, and somehow makes effector T cells more sensitive to stimulation by specific antigen.