Trafficking and migration in tolerance

PURPOSE OF REVIEW: Understanding trafficking and migration of antigen-presenting cells and T cells is important to uncover the anatomic domains where lymphocytes interact with alloantigen during the tolerization process and whether the interactions for immunity and rejection are anatomically separate from those important for tolerance. RECENT FINDINGS: Lymphocyte trafficking and migration are seminal events that determine the outcome of the immune response, from initial priming to either effector responses or tolerance. Recent evidence shows that dendritic cell migration to distinct anatomic sites is likewise necessary in the choice between rejection versus tolerance to an allograft. As a result, identifying the precise lymphoid organs where lymphocytes interact with alloantigen-presenting cells under systemic immunosuppression is critical for manipulating the immune response towards the development of tolerance. SUMMARY: This paper summarizes recent findings on leukocyte trafficking to distinct anatomic sites that are responsible for the induction and maintenance of tolerance and compares these findings to studies that analyze leukocyte migration during priming and rejection. The interpretations presented here illustrate that similar mechanisms govern migration of both beneficial and damaging cell subsets to the site of engraftment and secondary lymphoid organs. The concomitant therapeutic implications are discussed.