High expression of ILT3 and ILT4 is a general feature of tolerogenic dendritic cells.
The direct interaction between antigen specific CD8(+) CD28(-) T suppressor cells (T(S)) with dendritic cells (DC) results in the tolerization of DC by inducing the upregulation of immunologlobulin like transcript 3 (ILT3) and ILT4. We show here that such tolerogenic DC anergize alloreactive CD4(+) CD45RO(+) CD25(+) T cells converting them into regulatory T cells (T(R)), which in turn, continue the cascade of suppression by tolerizing other DC. Interleukin 10 (IL-10) and interferon-alpha (IFN-alpha) also induce ILT3 and ILT4 upregulation in DC, rendering them tolerogenic. This implies a common mechanism of DC-mediated suppression. This finding and the observation that in organ allograft recipients quiescence is associated with the presence in the circulation of donor-specific T(S) and T(R) emphasize the importance of the cross talk between tolerogenic DC and T cells in suppression of the immune response.
Manavalan
John S
JS
Department of Pathology and Internal Medicine, Columbia University, 630 West 168th Street, P&S 14-401, New York, NY 10032, USA.
Rossi
Paola C
PC
Vlad
George
G
Piazza
Flavia
F
Yarilina
Anna
A
Cortesini
Raffaello
R
Mancini
Donna
D
Suciu-Foca
Nicole
N
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D002762:Cholecalciferol / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation; D023001:Transplantation Tolerance
D016207:Cytokines; D006684:HLA-DR Antigens; D007377:Interleukin-3; C491341:LILRB2 protein, human; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D002762:Cholecalciferol; D015847:Interleukin-4; D017493:Leukocyte Common Antigens