Generation and function of antigen-specific suppressor and regulatory T cells

The identification and characterization of regulatory and suppressor T cells that control immune responsiveness to self and non-self antigens has become the focus of innumerable studies. There are two broad categories of naturally occurring and induced CD4(+)CD25(+) regulatory T cells. Naturally occurring T-R are antigen non-specific and interact directly with other T cells inhibiting their activation. Induced TR are either CD4(+)CD25(+) or CD8(+), produce immunosuppressive cytokines such as IL-10, act directly on other T cells or APC and are antigen specific in some but not in all systems. Finally, a distinct subset of T suppressor cells, characterized by their CD8(+)CD28(-) phenotype have been shown to be antigen-specific, recognizing HLA class I/peptide complexes. T, act directly on APC inducing the up-regulation of inhibitory receptors ILT3 and ILT4, which render the APC tolerogenic. Tolerized APC, which expresses high ILT3 and ILT4, trigger the generation of antigen-specific CD4(+) T, propagating antigen-specific suppression. Up-regulation of ILT3 and ILT4 appears to be a general characteristic of tolerogenic DC since it is also induced by use of vit D3, IL-10 and/or IFN-alpha. The clinical relevance of these inhibitory receptors is in the maintenance of transplantation tolerance as well as in progression of AIDS has been demonstrated. (C) 2003 Elsevier B.V. All rights reserved.