Role of Regulatory/Suppressor T Cells in Immune Responses

Abstract

Although the concept of suppression mediated by T lymphocytes was originally proposed more than 30 years ago, studies over the past 15 years in animal models of autoimmunity have rekindled interest in the existence of a unique lineage of thymic-derived T lymphocytes that specifically suppress immune responses. This population of naturally occurring suppressor T cells can be identified by its co-expression of the CD4 and CD25 antigens, as well as by the presence of the transcription factor, Foxp3. CD4⁺CD25⁺Foxp3⁺ T cells (∼10% of CD4⁺ T cells) are now commonly referred to as T regulatory cells (Treg). Our group was among the first to demonstrate that Treg cells were potent suppressors of the activation of both CD4 and CD8 lymphocytes in vitro, in response both to polyclonal stimuli and specific antigens by an as-yet unknown cell contact-dependent mechanism. A population with identical phenotypic and functional properties has also been identified in man. While the initial studies focused on the effects of these cells in suppressing responses to autoantigens, Treg have now been shown to play a central role in controlling the immune responses to alloantigens, tumor-associated antigens, allergens, and, most importantly, pathogen-derived antigens (Fig. 22.1). Although considerable progress has been made in this field, a number of central issues remain to be addressed, including (i) the molecular basis for cell-contact mediated suppression; (ii) the relationship (if any) between the in vitro studies and the mechanisms whereby Treg suppress in vivo, and (iii) how the function of these Treg can be manipulated in vivo so as either to diminish or enhance their function.