Selection and behavior of CD4⁺ CD25⁺ T cells in vivo: Lessons from T cell receptor transgenic models

Despite great interest in CD4⁺ CD25⁺ suppressor T cells, many of the fundamental properties of these cells remain enigmatic. This is in part due to experimental limitations inherent to the study of polyclonal suppressor T cells, and the extensive use of in vitro assays. This review article intends to outline recent advances in our understanding of the biology of suppressor T cells that have emerged from the analysis of T cell receptor (TCR) transgenic models. Several laboratories have taken advantage of model systems in which suppressor T cells of defined antigen-specificity are naturally selected in order to characterize the selection and behavior of these cells in vivo. In addition to providing valuable insights into the mechanism of differentiation of suppressor T cells, these systems now offer new possibilities for understanding the mode of action of suppressor T cells. For example, adoptive transfer of small numbers of ex vivo isolated TCR transgenic suppressor T cells allows for the visualization of the fate of such cells when confronted with cognate antigen in a quasi-normal, nonlymphopenic environment. Characteristic features of the currently available TCR transgenic models of suppressor T cells will be highlighted, and particular issues pertaining to the differentiation, function, and homeostasis of this T cell subset that have emerged from these models will be discussed.