T-bet is required for optimal proinflammatory CD4+ T-cell trafficking

被引:211
作者
Lord, GM
Rao, RM
Choe, H
Sullivan, BM
Lichtman, AH
Luscinskas, FW
Glimcher, LH
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
[2] Hammersmith Hosp, Imperial Coll Sch Med, Eric Bywaters Ctr Vasc Inflammat, London, England
[3] Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp, Boston, MA USA
[4] Harvard Univ, Sch Med, Dept Med, Boston, MA USA
[5] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA
[6] Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Ctr Excellence Vasc Biol, Boston, MA 02115 USA
基金
英国医学研究理事会;
关键词
D O I
10.1182/blood-2005-04-1393
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Inflammatory responses are controlled by T helper 1 (Th1) lymphocytes. An important function of this polarity is the ability of T cells to traffick appropriately in vivo. This differential trafficking is dependent upon the binding of P-selectin glycoprotein ligand-1 to P- and E-selectin on inflamed endothelium as well as the expression of specific chemokine receptors. Here we show that in the absence of T-box expressed in T cells (T-bet), selective migration of T cells in vivo is completely abrogated and that T-bet regulates the binding of CD4(+) T cells to P-selectin. T-bet is also required for the expression of the chemokine receptor CXCR3. Thus, T-bet controls Th1-cell migration to inflammatory sites, which has fundamental consequences for the control of immunologic disease.
引用
收藏
页码:3432 / 3439
页数:8
相关论文
共 51 条
[1]   Functional diversity of helper T lymphocytes [J].
Abbas, AK ;
Murphy, KM ;
Sher, A .
NATURE, 1996, 383 (6603) :787-793
[2]   P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues [J].
Austrup, F ;
Vestweber, D ;
Borges, E ;
Lohning, M ;
Brauer, R ;
Herz, U ;
Renz, H ;
Hallmann, R ;
Scheffold, A ;
Radbruch, A ;
Hamann, A .
NATURE, 1997, 385 (6611) :81-83
[3]   Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis [J].
Bettelli, E ;
Sullivan, B ;
Szabo, SJ ;
Sobel, RA ;
Glimcher, H ;
Kuchroo, VK .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (01) :79-87
[4]   Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s [J].
Bonecchi, R ;
Bianchi, G ;
Bordignon, PP ;
D'Ambrosio, D ;
Lang, R ;
Borsatti, A ;
Sozzani, S ;
Allavena, P ;
Gray, PA ;
Mantovani, A ;
Sinigaglia, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (01) :129-134
[5]   Chemokines and the arrest of lymphocytes rolling under flow conditions [J].
Campbell, JJ ;
Hedrick, J ;
Zlotnik, A ;
Siani, MA ;
Thompson, DA ;
Butcher, EC .
SCIENCE, 1998, 279 (5349) :381-384
[6]   Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines [J].
Cinamon, G ;
Shinder, V ;
Alon, R .
NATURE IMMUNOLOGY, 2001, 2 (06) :515-522
[7]   Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry [J].
Farzan, M ;
Mirzabekov, T ;
Kolchinsky, P ;
Wyatt, R ;
Cayabyab, M ;
Gerard, NP ;
Gerard, C ;
Sodroski, J ;
Choe, H .
CELL, 1999, 96 (05) :667-676
[8]   β cells are responsible for CXCR3-mediated T-cell infiltration in insulitis [J].
Frigerio, S ;
Junt, T ;
Lu, B ;
Gerard, C ;
Zumsteg, U ;
Holländer, GA ;
Piali, L .
NATURE MEDICINE, 2002, 8 (12) :1414-1420
[9]  
Gironella M, 2002, J LEUKOCYTE BIOL, V72, P56
[10]   P-selectin glycoprotein ligand 1 (PSGL-1) is a physiological ligand for E-selectin in mediating T helper 1 lymphocyte migration [J].
Hirata, T ;
Merrill-Skoloff, G ;
Aab, M ;
Yang, J ;
Furie, BC ;
Furie, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (11) :1669-1675