Immunosuppressive activity of recombinant ILT3

被引:10
作者
Vlad, George [1 ]
Liu, Zhuoru [1 ]
Zhang, Qing-Yin [1 ]
Cortesini, Raffaello [1 ]
Suciu-Foca, Nicole [1 ]
机构
[1] Columbia Univ, Dept Pathol, New York, NY 10032 USA
关键词
CD8(+) T suppressor cells; tolerogenic APC; membrane ILT3; soluble ILT3;
D O I
10.1016/j.intimp.2006.07.017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tolerogenic antigen presenting cells (APC) are characterized by high expression of the inhibitory receptors ILT3 and ILT4. We have engineered ILT3 and ILT4 cytoplasmic deletion mutants (ILT3delta and ILT4delta), which were transfected in the dendritic-like cell line KG 1, to investigate ILT3 and ILT4's capacity to signal extracellularly. KG1.ILT3delta, similar to untruncated ILT3, inhibits T cell responses such as proliferation and cell-mediated cytotoxicity. In contrast, KG1.ILT4delta lost the suppressive activity of untruncated ILT4. This indicates that the inhibitory function of ILT4 relies entirely on the cytoplasmic region containing ITIM motifs. We further demonstrated that recombinant soluble ILT3 inhibits T helper and cytotoxic function while inducing the differentiation of CD8(+) Ts cells. Hence, Ts modulated APC function inducing inhibitory receptors, which in turn elicit the generation of Ts. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:1889 / 1894
页数:6
相关论文
共 23 条
[1]   Interleukin 10 regulates cell surface and soluble LIR-2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro [J].
Beinhauer, BG ;
McBride, JM ;
Graf, P ;
Pursch, E ;
Bongers, M ;
Rogy, M ;
Korthauer, U ;
de Vries, JE ;
Aversa, G ;
Jung, T .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (01) :74-80
[2]   Natural versus adaptive regulatory T cells [J].
Bluestone, JA ;
Abbas, AK .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (03) :253-257
[3]   Tolerization of dendritic cells by TS cells:: the crucial role of inhibitory receptors ILT3 and ILT4 [J].
Chang, CC ;
Ciubotariu, R ;
Manavalan, JS ;
Yuan, J ;
Colovai, AI ;
Piazza, F ;
Lederman, S ;
Colonna, M ;
Cortesini, R ;
Dalla-Favera, R ;
Suciu-Foca, N .
NATURE IMMUNOLOGY, 2002, 3 (03) :237-243
[4]  
Ciubotariu R, 1998, J IMMUNOL, V161, P5193
[5]   Detection of T suppressor cells in patients with organ allografts [J].
Ciubotariu, R ;
Vasilescu, R ;
Ho, E ;
Cinti, P ;
Cancedda, C ;
Poli, L ;
Late, M ;
Liu, ZR ;
Berloco, P ;
Cortesini, R ;
Cortesini, NSF .
HUMAN IMMUNOLOGY, 2001, 62 (01) :15-20
[6]   CD8+CD28- T suppressor cells and the induction of antigen-specific, antigen-presenting cell-mediated suppression of Th reactivity [J].
Cortesini, R ;
LeMaoult, J ;
Ciubotariu, R ;
Cortesini, NSF .
IMMUNOLOGICAL REVIEWS, 2001, 182 :201-206
[7]   Regulatory T cell lineage specification by the forkhead transcription factor FoxP3 [J].
Fontenot, JD ;
Rasmussen, JP ;
Williams, LM ;
Dooley, JL ;
Farr, AG ;
Rudensky, AY .
IMMUNITY, 2005, 22 (03) :329-341
[8]   Induction of MHC Class I restricted human suppressor T cells by peptide priming in vitro [J].
Jiang, SP ;
Tugulea, S ;
Pennesi, G ;
Liu, ZR ;
Mulder, A ;
Lederman, S ;
Harris, P ;
Cortesini, R ;
Suciu-Foca, N .
HUMAN IMMUNOLOGY, 1998, 59 (11) :690-699
[9]   Recombinant Ig-like transcript 3-Fc modulates T cell responses via induction of th anergy and differentiation of CD8+ T suppressor cells [J].
Kim-Schulze, Seunghee ;
Scotto, Luigi ;
Vlad, George ;
Piazza, Flavia ;
Lin, Hana ;
Liu, Zhuoru ;
Cortesini, Raffaello ;
Suciu-Foca, Nicole .
JOURNAL OF IMMUNOLOGY, 2006, 176 (05) :2790-2798
[10]  
Li JF, 1999, J IMMUNOL, V163, P6386