Immune functions fully depend on proper relocation of leukocytes, a process controlled by adhesion molecules and a myriad of leukocyte chemoattractant cytokines, termed chemokines. Chemokine research developed rapidly from the original discovery of their involvement in inflammatory responses to the current understanding that nothing happens without them. All aspects of immunity, including hematopoiesis and immune surveillance, as well as initiation and control of adaptive immune responses, are controlled by chemokines. Our article summarizes current findings about lymphocyte responses to chemokines, which is a subject that had a slow start but rapidly advanced in recent years. We have now a much clearer idea about the mechanisms of cell recruitment that guide T and B cells along their multifaceted routes of maturation and immune defense, and this may help explain why immunologists with chemokine-unrelated expertise took interest in our discussion.

We like to emphasize that the successful completion of T and B cell functions fully depends on their correct recruitment and localization within diverse microenvironments. This does not only include mere migratory processes, such as the exit of newly generated T and B cells from their places of origin (bone marrow, thymus) or their extravasation into lymphoid and peripheral tissues, but also cell-to-cell contacts that enable antigen recognition. The firm link between mobility and function will be an important consideration in future lymphocyte research. Also, chemokine-based intervention of cell recruitment is a current strategy for the development of novel anti-inflammatory therapy.

Protection of our body against countless pathogens and harmful substances is ensured by a complex system of immune cells. Successful immunity fully depends on efficient elaboration of inflammatory leukocytes and their precise guidance to the sites of pathogen entry or tissue destruction. Chemokines play an essential role in these processes. Our review summarizes the involvement of chemokines in the specific area of immunity, which is characterized by antigen specificity and immune memory.

We have a long-standing interest in chemokine research, dating back to neutrophil responses to IL-8 and related chemokines. In 1996, we were able to show that T cells, after proper stimulation, also respond to chemokines. Since then, we have investigated inflammatory as well as homeostatic aspects of T cell traffic in lymph nodes and peripheral tissues.

Pius Loetscher, P.D., Ph.D.
Theodor-Kocher Institute
University of Bern
Bern, Switzerland