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 T R 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 S 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 R 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-α. The clinical relevance of these inhibitory receptors is in the maintenance of transplantation tolerance as well as in progression of AIDS has been demonstrated.