T-Cell Costimulation and Coinhibition in Atherosclerosis

被引:146
作者
Gotsman, Israel [2 ]
Sharpe, Arlene H. [3 ]
Lichtman, Andrew H. [1 ,3 ,4 ,5 ]
机构
[1] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[2] Hadassah Univ Hosp, Inst Heart, IL-91120 Jerusalem, Israel
[3] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Div Immunol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Div Vasc Res, Boston, MA 02115 USA
关键词
atherosclerosis; costimulation; coinhibition; T lymphocytes;
D O I
10.1161/CIRCRESAHA.108.182428
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Evidence from many human and rodent studies has established that T lymphocytes enhance inflammation in atherosclerotic plaques and contribute to lesion progression and remodeling. Recent work also indicates that regulatory T cells are important in limiting proatherogenic T-cell responses. Given the important role of T cells in atherosclerosis, there is a need to fully understand how proatherogenic T cells are activated and regulated. Antigen-dependent activation of nave T cells, leading to clonal expansion and effector T-cell differentiation, and effector and memory T cells, is enhanced by signals provided by costimulatory molecules expressed by antigen presenting cells, which bind to receptors on the T cells. In addition, T-cell responses to antigen are negatively regulated by coinhibitory molecules expressed by antigen-presenting cells, which bind to receptors on T cells. Two major families of costimulatory molecules include the B7 and the tumor necrosis factor (TNF) families. These molecules bind to receptors on T cells belonging to the CD28 or TNF receptor families, respectively. The best-defined coinhibitors and their receptors belong to the B7 and CD28 families. Recent work has begun to define how these T-cell costimulatory and coinhibitory pathways influence atherosclerosis, largely in mouse models of the disease. Profound effects are attributable to molecules in both the B7/CD28 (B7-1/2, ICOS, and PDL-1/2) and the TNF/TNF receptor (CD40, OX40, and CD137) families. One emerging theme is that both pathogenic effector T-cell responses and regulatory T cells are influenced by overlapping sets of costimulators and coinhibitors. These complexities must be considered as immunotherapeutic approaches for atherosclerotic disease are developed. (Circ Res. 2008; 103: 1220-1231.)
引用
收藏
页码:1220 / 1231
页数:12
相关论文
共 108 条
[1]   A functional role for inducible costimulator (ICOS) in atherosclerosis [J].
Afek, A ;
Harats, D ;
Roth, A ;
Keren, G ;
George, J .
ATHEROSCLEROSIS, 2005, 183 (01) :57-63
[2]   Evidence for the involvement of T cell costimulation through the B-7/CD28 pathway in atherosclerotic plaques from apolipoprotein E knockout mice [J].
Afek, A ;
Harats, D ;
Roth, A ;
Keren, G ;
George, J .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2004, 76 (03) :219-223
[3]   Natural regulatory T cells control the development of atherosclerosis in mice [J].
Ait-Oufella, H ;
Salomon, BL ;
Potteaux, S ;
Robertson, AKL ;
Gourdy, P ;
Zoll, J ;
Merval, R ;
Esposito, B ;
Cohen, JL ;
Fisson, S ;
Flavell, RA ;
Hansson, GK ;
Klatzmann, D ;
Tedgui, A ;
Mallat, Z .
NATURE MEDICINE, 2006, 12 (02) :178-180
[4]  
Akbari O, 2002, NAT MED, V8, P1024, DOI 10.1038/nm745
[5]   Restoring function in exhausted CD8 T cells during chronic viral infection [J].
Barber, DL ;
Wherry, EJ ;
Masopust, D ;
Zhu, BG ;
Allison, JP ;
Sharpe, AH ;
Freeman, GJ ;
Ahmed, R .
NATURE, 2006, 439 (7077) :682-687
[6]   Atherogenesis in mice does not require CD40 ligand from bone marrow-derived cells [J].
Bavendiek, U ;
Zirlik, A ;
LaClair, S ;
MacFarlane, L ;
Libby, P ;
Schönbeck, U .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (06) :1244-1249
[7]   Innate and acquired immunity in atherogenesis [J].
Binder, CJ ;
Chang, MK ;
Shaw, PX ;
Miller, YI ;
Hartvigsen, K ;
Dewan, A ;
Witztum, JL .
NATURE MEDICINE, 2002, 8 (11) :1218-1226
[8]   ICOS+Th cells produce distinct cytokines in different mucosal immune responses [J].
Bonhagen, K ;
Liesenfeld, O ;
Stadecker, MJ ;
Hutloff, A ;
Erb, K ;
Coyle, AJ ;
Lipp, M ;
Kroczek, RA ;
Kamradt, T .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (02) :392-401
[9]   B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation [J].
Borriello, F ;
Sethna, MP ;
Boyd, SD ;
Schweitzer, AN ;
Tivol, EA ;
Jacoby, D ;
Strom, TB ;
Simpson, EM ;
Freeman, GJ ;
Sharpe, AH .
IMMUNITY, 1997, 6 (03) :303-313
[10]   Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells [J].
Bour-Jordan, H ;
Salomon, BL ;
Thompson, HL ;
Szot, GL ;
Bernhard, MR ;
Bluestone, JA .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (07) :979-987