Migration Rules: Functional Properties of Naive and Effector/Memory-Like Regulatory T Cell Subsets

摘要

Suppressor T cells were first described in the early 1970s, but since the hypothetical soluble suppressor factor could not be identified on a molecular level and since appropriate cellular markers were lacking, the suppressor T cell concept vanished for a long time. The discovery by Sakaguchi and co-workers, that the adoptive transfer of CD25~+CD4~+-depleted T cells induced several organ-specific autoimmune diseases in immunodeficient recipients, put the suppressor T cell model back into the focus of many immunologists, CD25~+CD4~+ T cells were named regulatory T cells (Treg) and since then have been intensively characterized by many groups. It has now been well documented in a var iety of models that CD25~+CD4~+ Tr egs, in addition to cell-intr insic peripheral tolerance mechanisms such as anergy induction and peripheral deletion, play indispensable roles in the maintenance of natural self-tolerance, in averting autoimmune responses as well as in controlling inflammatory reactions. However,a number of fundamental questions concerning their origin, mechanism of action, and the sites of suppression remain elusive and are currently a matter of debate. Notably, the potential heterogeneity of Tregs with respect to phenotype and function deserves attention and is a major issue discussed in this review.