Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4.
Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells. We show here that CD8+CD28(-) alloantigen-specific T suppressor (TS) cells induce the up-regulation of ILT3 and ILT4 on monocytes and dendritic cells, rendering these antigen-presenting cells (APCs) tolerogenic. Tolerogenic APCs show reduced expression of costimulatory molecules and induce antigen-specific unresponsiveness in CD4+ T helper cells. Studies of human heart transplant recipients showed that rejection-free patients have circulating TS cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs. These findings demonstrate an important mechanism of immune regulation.
Chang
C C
CC
Department of Pathology, Columbia University, New York, NY 10032, USA.
Ciubotariu
R
R
Manavalan
J S
JS
Yuan
J
J
Colovai
A I
AI
Piazza
F
F
Lederman
S
S
Colonna
M
M
Cortesini
R
R
Dalla-Favera
R
R
Suciu-Foca
N
N
D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000502:physiology; D018106:CD28 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D008562:Membrane Glycoproteins; D016328:NF-kappa B / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D018106:CD28 Antigens; D016827:CD8 Antigens; C491341:LILRB2 protein, human; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic