Chemokine Receptors and Lymphocyte Trafficking

The ordered movement of lymphocytes through and positioning within lymphoid organs and peripheral sites is controlled by adhesion molecules together with chemokines and their receptors. Chemokine-mediated lymphocyte migration is critical for establishing the architecture of lymphoid organs and many aspects of lymphocyte function, including lymphocyte development, activation, and effector activity. Of the 19 chemokine receptors described in humans, all have been reported to be expressed on lymphocytes, and the expression pattern of chemokine receptors can itself be used to define and characterize lymphocyte subsets. For example, by using chemokine receptors, memory T cells can be split into distinct populations, such as central and effector memory T cells; and T helper 1 (Th1) and T helper 2 (Th2) cells exhibit distinguishable patterns of chemokine receptor expression, which can be used to study Th1/Th2 differentiation. Beyond their physiologic roles, chemokine receptors on lymphocytes are exploited by pathogens, such as in the use of CCR5 and CXCR4 by HIV-1 as coreceptors for viral entry. In this chapter, we will focus on the roles of chemokine receptors in lymphocyte trafficking in lymphoid organs and peripheral tissues and how understanding the chemokine system has shed light on larger issues in lymphocyte biology. We will discuss the roles of chemokines and chemokine receptors during the life cycles of lymphocytes—from early development through the acquisition of memory and effector functions.