Double-negative regulatory T cells - Non-conventional regulators

被引:80
作者
Thomson, Christopher W.
Lee, Boris P-L
Zhang, Li
机构
[1] Univ Toronto, MaRS Ctr, Hlth Network,Toronto Gen Res Inst, Dept Lab Med & Pathobiol,Multiorgan Transplantat, Toronto, ON, Canada
[2] Univ Toronto, Dept Immunol, Toronto, ON, Canada
关键词
regulatory T cells; suppression; tolerance; transplantation; cancer immunotherapy;
D O I
10.1385/IR:35:1:163
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The crucial role of regulatory T (Treg) cells in self-tolerance and downregulating immune responses has been clearly established. Numerous different Treg subsets have been identified that possess distinct phenotypes and functions in various disease models. Among these subsets, alpha beta-TCR(+)CD3(+)CD4(-)CD8(-) double-negative (DN) Treg cells have been shown to be able to inhibit a variety of immune responses in part via direct killing of effector T cells in an antigen-specific manner in both mice and humans. This was shown to occur at least partially by acquisition of MHC-peptide complexes from antigen-presenting cells (APCs) and subsequent Fas/Fas-ligand interactions. In addition, DN Treg cells have been shown to express several molecules uncommon to other Treg cell subsets, such as IFN-gamma, TNF-alpha, Ly6A, FcR gamma, and CXCR5, which may contribute to their unique regulatory ability. Understanding the development and regulatory functions of DN Treg cells may elucidate the etiology for loss of self-tolerance and serve as a therapeutic modality for various diseases. This review will summarize the characteristics, developmental pathways, and mechanisms of action of DN Treg cells, as well as their role in transplant tolerance, autoimmunity, and anticancer immunity.
引用
收藏
页码:163 / 177
页数:15
相关论文
共 90 条
[1]  
ABRAHAM VS, 1992, J IMMUNOL, V148, P3746
[2]   Role of regulatory T cells in allergy and asthma [J].
Akbari, O ;
Stock, P ;
DeKruyff, RH ;
Umetsu, DT .
CURRENT OPINION IN IMMUNOLOGY, 2003, 15 (06) :627-633
[3]   In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines [J].
Ansel, KM ;
McHeyzer-Williams, LJ ;
Ngo, VN ;
McHeyzer-Williams, MG ;
Cyster, JG .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (08) :1123-1134
[4]   An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation [J].
Asseman, C ;
Mauze, S ;
Leach, MW ;
Coffman, RL ;
Powrie, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (07) :995-1003
[5]   Regulatory T cells under scrutiny [J].
Bach, JF .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (03) :189-198
[6]   B cells acquire antigen from target cells after synapse formation [J].
Batista, FD ;
Iber, D ;
Neuberger, MS .
NATURE, 2001, 411 (6836) :489-494
[7]   The role of cytokines (and not only) in inducing and expanding T regulatory type 1 cells [J].
Battaglia, M ;
Roncarolo, MG .
TRANSPLANTATION, 2004, 77 (01) :S16-S18
[8]   MRL/lpr CD4(-)CD8(-) and CD8(+) T cells, respectively, mediate Fas-dependent and perforin cytotoxic pathways [J].
Benihoud, K ;
Bonardelle, D ;
Bobe, P ;
Kiger, N .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (02) :415-420
[9]   Infusion of in vitro-generated DN T regulatory cells induces permanent cardiac allograft survival in mice [J].
Chen, W ;
Ford, MS ;
Young, KJ ;
Zhang, L .
TRANSPLANTATION PROCEEDINGS, 2003, 35 (07) :2479-2480
[10]   Donor lymphocyte infusion induces long-term donor-specific cardiac xenograft survival through activation of recipient double-negative regulatory T cells [J].
Chen, WH ;
Zhou, DJ ;
Torrealba, JR ;
Waddell, TK ;
Grant, D ;
Zhang, L .
JOURNAL OF IMMUNOLOGY, 2005, 175 (05) :3409-3416