Cross-tolerance: A Pathway for Inducing Tolerance to Peripheral Tissue Antigens

Tlymphocytes develop within the thymus, where they are positively selected for self-restriction and purged of cells exhibiting strong reactivity to self-antigens presented within this microenvironment. Mature lymphocytes then enter the peripheral lymphoid pool, where they recirculate between the various secondary lymphoid organs, including the spleen and the lymph nodes that drain peripheral tissues (1). It is almost exclusively within these lymphoid tissues that T lymphocytes first encounter antigen. The rapid recirculation of the total lymphocyte repertoire within the relatively confined secondary lymphoid compartment, in combination with the effective movement of antigens from peripheral sites to draining lymph nodes, permits highly efficient surveillance for infection throughout the whole organism. Thus, the secondary lymphoid organs effectively bring together the key players required for immunity; notably the T cells, their target antigen, and, importantly, the APCs. It is the APCs that simultaneously provide a crucial scaffold for effective recognition of...