Chemokines: control of primary and memory T-cell traffic

Motility is a hallmark of leukocytes, and breakdown in the control of migration contributes to many inflammatory diseases. Chemotactic migration of leukocytes largely depends on adhesive interaction with the substratum and recognition of a chemoattractant gradient. Chemokines are secreted proteins and have emerged as key controllers of integrin function and cell locomotion. Numerous distinct chemokines exist that target all types of leukocytes, including hematopoietic precursors, leukocytes of the innate immune system, as well as naive memory, and effector lymphocytes. The combinatorial diversity in responsiveness to chemokines ensures the proper tissue distribution of distinct leukocyte subsets under normal and pathological conditions. Inflammatory chemokines are readily detected in lesional tissue and local cellular infiltrates carry corresponding chemokine receptors. Blocking of inflammatory chemokines represents a promising strategy for the development of novel anti-inflammatory therapeutics. This review focuses on a separate class of chemokines, termed homeostatic chemokines, with steady-state production at diverse sites, including primary and secondary lymphoid tissues as well as peripheral (extralymphoid) tissues. More precisely, we discuss the chemokines involved in T-cell traffic during the initiation of adaptive immunity and compare the distinct migration properties of short-lived effector T cells and long-lived memory T cells. Memory T cells are currently classified according to the presence of the lymph node-homing receptor CCR7 into CCR7+ central memory T (T(CM)) cells and CCR7- effector memory T (T(EM)) cells. For better understanding memory T-cell function, we propose the distinction of a third category, termed peripheral immune surveillance T (T(PS)) cells, which typically reside in healthy peripheral tissues, such as skin, lung, and gastrointestinal tract. Localization and relocation of memory T cells is strictly related to their function in recall responses. Therefore, detailed knowledge of their generation and tissue distribution may help to design better vaccination strategies.