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-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.
Suciu-Foca
Nicole
N
Columbia University, Department of Pathology, 630 West 168 Street--P&S 14-401, New York, NY 10032, USA. ns20@columbia.edu
Manavalan
John S
JS
Cortesini
Raffaello
R
D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D023001:Transplantation Tolerance
D000941:Antigens; C491341:LILRB2 protein, human; C107907:LILRB4 protein, human; C408902:MHC binding peptide; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic