Unique gene expression program of human germinal center T helper cells

被引:205
作者
Kim, CH
Lim, HW
Kim, JR
Rott, L
Hillsamer, P
Butcher, EC
机构
[1] Purdue Univ, Lab Immunol & Hematopoiesis, Dept Pathobiol, Purdue Canc Ctr,Bindley Biosci Ctr, W Lafayette, IN 47907 USA
[2] Purdue Univ, Biochem & Mol Biol Program, W Lafayette, IN 47907 USA
[3] Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Stanford, CA USA
[4] Vet Affairs Palo Alto Hlth Care Syst, Ctr Mol Biol & Med, Palo Alto, CA USA
[5] Sagamore Surg Ctr, Lafayette, IN USA
关键词
D O I
10.1182/blood-2004-03-1206
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Gene expression profiling was used to compare the gene expression patterns of human germinal center (GC) T helper (Th) cells with other CD4(+) T-cell subsets (naive, central, and effector memory T cells). GC-Th cells, specifically localized in germinal centers to help B cells, are distantly related to central and effector memory T cells in global gene expression profiles. GC-Th cells displayed substantial differences in mRNA for adhesion molecules, chemoattractant receptors, and cytokines compared with other populations. Distinct expression of transcriptional factors by GC-Th cells is consistent with the hypothesis that they may be different from other T cells in cell lineage. Interestingly, CXCL13, a critical chemokine for B-cell entry to lymphoid follicles, is one of the most highly up-regulated genes in GC-Th cells. GC-Th cells (but not other T cells) produce and secrete large amounts of functional CXCL13 upon T-cell receptor activation, a process that is dependent on costimulation, requires translation and transcription, and is dramatically enhanced by activation in the presence of GC-B cells. This study revealed for the first time the unique gene expression program of GC-Th cells. (C) 2004 by The American Society of Hematology.
引用
收藏
页码:1952 / 1960
页数:9
相关论文
共 52 条
[1]   Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice [J].
Alimzhanov, MB ;
Kuprash, DV ;
KoscoVilbois, MH ;
Luz, A ;
Turetskaya, RL ;
Tarakhovsky, A ;
Rajewsky, K ;
Nedospasov, SA ;
Pfeffer, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (17) :9302-9307
[2]   Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].
Alizadeh, AA ;
Eisen, MB ;
Davis, RE ;
Ma, C ;
Lossos, IS ;
Rosenwald, A ;
Boldrick, JG ;
Sabet, H ;
Tran, T ;
Yu, X ;
Powell, JI ;
Yang, LM ;
Marti, GE ;
Moore, T ;
Hudson, J ;
Lu, LS ;
Lewis, DB ;
Tibshirani, R ;
Sherlock, G ;
Chan, WC ;
Greiner, TC ;
Weisenburger, DD ;
Armitage, JO ;
Warnke, R ;
Levy, R ;
Wilson, W ;
Grever, MR ;
Byrd, JC ;
Botstein, D ;
Brown, PO ;
Staudt, LM .
NATURE, 2000, 403 (6769) :503-511
[3]   A chemokine-driven positive feedback loop organizes lymphoid follicles [J].
Ansel, KM ;
Ngo, VN ;
Hyman, PL ;
Luther, SA ;
Förster, R ;
Sedgwick, JD ;
Browning, JL ;
Lipp, M ;
Cyster, JG .
NATURE, 2000, 406 (6793) :309-314
[4]   Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production [J].
Breitfeld, D ;
Ohl, L ;
Kremmer, E ;
Ellwart, J ;
Sallusto, F ;
Lipp, M ;
Förster, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (11) :1545-1551
[5]   Separable effector T cell populations specialized for B cell help or tissue inflammation [J].
Campbell, DJ ;
Kim, CH ;
Butcher, EC .
NATURE IMMUNOLOGY, 2001, 2 (09) :876-881
[6]   Cutting edge: Critical role of inducible costimulator in germinal center reactions [J].
Dong, C ;
Temann, UA ;
Flavell, RA .
JOURNAL OF IMMUNOLOGY, 2001, 166 (06) :3659-3662
[7]   Cluster analysis and display of genome-wide expression patterns [J].
Eisen, MB ;
Spellman, PT ;
Brown, PO ;
Botstein, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14863-14868
[8]   A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen [J].
Forster, R ;
Mattis, AE ;
Kremmer, E ;
Wolf, E ;
Brem, G ;
Lipp, M .
CELL, 1996, 87 (06) :1037-1047
[9]   Lymphotoxin-alpha (LT alpha) supports development of splenic follicular structure that is required for IgG responses [J].
Fu, YX ;
Molina, H ;
Matsumoto, M ;
Huang, GM ;
Min, JJ ;
Chaplin, DD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (12) :2111-2120
[10]  
Glimcher Laurie H., 2001, Journal of Clinical Investigation, V108, pS25