| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Rheumatology and Clinical Immunology, University Clinic Freiburg, Freiburg, Germany;
Department of Oncology and Hematology, University Clinic Freiburg, Freiburg, Germany;
Department of Neuropathology, University Clinic Freiburg, Freiburg, Germany;
Department of Pediatrics and Institute for Molecular Medicine Angello Nocivelli, University of Brescia, Brescia, Italy;
¶ Hopital Necker, Institut National de la Santé et de la Recherche Médicale Unité 429, Paris, France;
|| Childrens’ Hospital, Medical School Hannover, Hannover, Germany; and
# Department of Inflammation, Amgen, Thousand Oaks, CA 91320
ICOS is expressed on activated T cells and particularly on CXCR5+ follicular Th cells in germinal centers (GC). Its deletion leads to a profound deficiency in memory B cell formation and switched Ab response in humans. Here, we show that in ICOS-deficient patients the generation of GCs is severely disturbed, and the numbers of circulating CXCR5+CD45RO+ memory CD4 T cells are significantly reduced, indicating an essential role of ICOS in the differentiation of CXCR5+CD4 T cells. The GC-specific CD57+CXCR5+ subpopulation is virtually absent. In ICOS–/– mice, the decrease of circulating CXCR5+CD4 T cells reflects the reduction of CXCR5+ follicular Th cells in lymph nodes and spleen. Therefore, in concurrence with the absence of CXCR5+ T cells in the blood of CD40L-deficient patients, these data support the hypothesis that circulating CD57+CXCR5+ T cells are GC derived and thus may serve as a surrogate marker for the presence of functional GCs in humans.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was sponsored by Deutsche Forschungsgemeinschaft Grants SFB620 TP C1 (to K.W. and H.H.P.), TP C2, and Deutsche Forschungsgemeinschaft Grant GR1617/3 (both to B.G.), Grant 2004.124.1 by the Wilhelm Sander Stiftung (to K.W.), and European Grants EU-IMPAD-QLG1-CT-200101536 and 239/99 (to B.G.).
2 Address correspondence and reprint requests to Dr. Klaus Warnatz, Division of Rheumatology and Clinical Immunology, University Hospital Freiburg, Hugstetterstrasse 55, D-79106 Freiburg, Germany. E-mail address: klaus.warnatz{at}uniklinik-freiburg.de
3 Abbreviations used in this paper: GC, germinal center; TFH cells, follicular Th cells; HEL, hen egg lysozyme; MIF, mean intensity of fluorescence; wt, wild type.
This article has been cited by other articles:
|
|
 |
|
  M. Gigoux, J. Shang, Y. Pak, M. Xu, J. Choe, T. W. Mak, and W.-K. Suh Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase PNAS, December 1, 2009; 106(48): 20371 - 20376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Spolski and W. J. Leonard IL-21 and T follicular helper cells Int. Immunol., November 23, 2009; (2009) dxp112v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. L. King and M. Mohrs IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells J. Exp. Med., May 11, 2009; 206(5): 1001 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Takahashi, K. Matsumoto, H. Saito, T. Nanki, N. Miyasaka, T. Kobata, M. Azuma, S.-K. Lee, S. Mizutani, and T. Morio Impaired CD4 and CD8 Effector Function and Decreased Memory T Cell Populations in ICOS-Deficient Patients J. Immunol., May 1, 2009; 182(9): 5515 - 5527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Linterman, R. J. Rigby, Raphael. K. Wong, D. Yu, R. Brink, J. L. Cannons, P. L. Schwartzberg, M. C. Cook, G. D. Walters, and C. G. Vinuesa Follicular helper T cells are required for systemic autoimmunity J. Exp. Med., March 16, 2009; 206(3): 561 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-c. Lin, Y. Peng, L. A. Jones, P. H. Verardi, and T. D. Yilma Incorporation of CD40 Ligand into the Envelope of Pseudotyped Single-Cycle Simian Immunodeficiency Viruses Enhances Immunogenicity J. Virol., February 1, 2009; 83(3): 1216 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-L. Hu, D. P. Metz, J. Chung, G. Siu, and M. Zhang B7RP-1 Blockade Ameliorates Autoimmunity through Regulation of Follicular Helper T Cells J. Immunol., February 1, 2009; 182(3): 1421 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kamperschroer, D. M. Roberts, Y. Zhang, N.-p. Weng, and S. L. Swain SAP Enables T Cells to Help B Cells by a Mechanism Distinct from Th Cell Programming or CD40 Ligand Regulation J. Immunol., September 15, 2008; 181(6): 3994 - 4003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Travert, P. Ame-Thomas, C. Pangault, A. Morizot, O. Micheau, G. Semana, T. Lamy, T. Fest, K. Tarte, and T. Guillaudeux CD40 Ligand Protects from TRAIL-Induced Apoptosis in Follicular Lymphomas through NF-{kappa}B Activation and Up-Regulation of c-FLIP and Bcl-xL J. Immunol., July 15, 2008; 181(2): 1001 - 1011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Tesciuba, R. A. Shilling, M. D. Agarwal, H. S. Bandukwala, B. S. Clay, T. V. Moore, J. V. Weinstock, A. A. Welcher, and A. I. Sperling ICOS Costimulation Expands Th2 Immunity by Augmenting Migration of Lymphocytes to Draining Lymph Nodes J. Immunol., July 15, 2008; 181(2): 1019 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hawiger, E. Tran, W. Du, C. J. Booth, L. Wen, C. Dong, and R. A. Flavell ICOS Mediates the Development of Insulin-Dependent Diabetes Mellitus in Nonobese Diabetic Mice J. Immunol., March 1, 2008; 180(5): 3140 - 3147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. Bryant, C. S. Ma, D. T. Avery, Y. Li, K. L. Good, L. M. Corcoran, R. de Waal Malefyt, and S. G. Tangye Cytokine-Mediated Regulation of Human B Cell Differentiation into Ig-Secreting Cells: Predominant Role of IL-21 Produced by CXCR5+ T Follicular Helper Cells J. Immunol., December 15, 2007; 179(12): 8180 - 8190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Lim and C. H. Kim Loss of IL-7 Receptor {alpha} on CD4+ T Cells Defines Terminally Differentiated B Cell-Helping Effector T Cells in a B Cell-Rich Lymphoid Tissue J. Immunol., December 1, 2007; 179(11): 7448 - 7456. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
