Interleukin-2 Inhibits Germinal Center Formation by Limiting T Follicular Helper Cell Differentiation

被引:427
|
作者
Ballesteros-Tato, Andre [1 ]
Leon, Beatriz [1 ]
Graf, Beth A. [1 ]
Moquin, Amy [2 ]
Adams, Pamela Scott [2 ]
Lund, Frances E. [1 ]
Randall, Troy D. [1 ]
机构
[1] Univ Rochester, Dept Med, Div Allergy Immunol & Rheumatol, Rochester, NY 14642 USA
[2] Trudeau Inst Inc, Saranac Lake, NY 12983 USA
关键词
RECOMBINANT INTERLEUKIN-2; REGULATORY CELLS; IN-VIVO; B-CELLS; IL-2; MICE; AUTOIMMUNITY; ACTIVATION; EXPRESSION; FOLLICLES;
D O I
10.1016/j.immuni.2012.02.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T follicular helper (Tfh) cells promote T cell-dependent humoral immune responses by providing T cell help to B cells and by promoting germinal center (GC) formation and long-lived antibody responses. However, the cellular and molecular mechanisms that control Tfh cell differentiation in vivo are incompletely understood. Here we show that interleukin-2 (IL-2) administration impaired influenza-specific GCs, long-lived IgG responses, and Tfh cells. IL-2 did not directly inhibit GC formation, but instead suppressed the differentiation of Tfh cells, thereby hindering the maintenance of influenza-specific GC B cells. Our data demonstrate that IL-2 is a critical factor that regulates successful Tfh and B cell responses in vivo and regulates Tfh cell development.
引用
收藏
页码:847 / 856
页数:10
相关论文
共 50 条
  • [21] T Follicular Helper Cell Differentiation, Function, and Roles in Disease
    Crotty, Shane
    IMMUNITY, 2014, 41 (04) : 529 - 542
  • [22] Emerging Roles for MicroRNAs in T Follicular Helper Cell Differentiation
    Maul, Julia
    Baumjohann, Dirk
    TRENDS IN IMMUNOLOGY, 2016, 37 (05) : 297 - 309
  • [23] Notch Signaling Regulates Follicular Helper T Cell Differentiation
    Auderset, Floriane
    Schuster, Steffen
    Fasnacht, Nicolas
    Coutaz, Manuel
    Charmoy, Melanie
    Koch, Ute
    Favre, Stephanie
    Wilson, Anne
    Trottein, Francois
    Alexander, James
    Luther, Sanjiv A.
    MacDonald, H. Robson
    Radtke, Freddy
    Tacchini-Cottier, Fabienne
    JOURNAL OF IMMUNOLOGY, 2013, 191 (05): : 2344 - 2350
  • [24] Pulmonary Infection with Influenza A Virus Induces Site-Specific Germinal Center and T Follicular Helper Cell Responses
    Boyden, Alexander W.
    Legge, Kevin L.
    Waldschmidt, Thomas J.
    PLOS ONE, 2012, 7 (07):
  • [25] Impact of Chronic HIV/SIV Infection on T Follicular Helper Cell Subsets and Germinal Center Homeostasis
    Graff-Dubois, Stephanie
    Rouers, Angeline
    Moris, Arnaud
    FRONTIERS IN IMMUNOLOGY, 2016, 7
  • [26] Limiting dilution analysis of interleukin-2 producing helper T-cell frequencies as a tool in allogeneic hematopoietic cell transplantation
    Petersen, SL
    Sidorov, IA
    Russell, CA
    Dickmeiss, E
    Vindelov, LL
    TRANSPLANTATION, 2005, 80 (05) : 573 - 581
  • [27] Interleukin-1 regulates follicular T cells during the germinal center reaction
    Belbezier, Aude
    Engeroff, Paul
    Fourcade, Gwladys
    Vantomme, Helene
    Vaineau, Romain
    Gouritin, Bruno
    Bellier, Bertrand
    Brocheriou, Isabelle
    Tchitchek, Nicolas
    Graff-Dubois, Stephanie
    Klatzmann, David
    FRONTIERS IN IMMUNOLOGY, 2024, 15
  • [28] Histone methyltransferase Nsd2 is required for follicular helper T cell differentiation
    Long, Xuehui
    Zhang, Le
    Zhang, Yang
    Min, Min
    Lin, Bichun
    Chen, Jingjing
    Ma, Xiaojie
    Zhai, Sulan
    Cai, Zhenming
    Liu, Yingxia
    Lu, Yanlai
    Che, Nan
    Tan, Wenfeng
    Qin, Jun
    Wang, Xiaoming
    JOURNAL OF EXPERIMENTAL MEDICINE, 2020, 217 (01):
  • [29] T-cell-derived IFN-γ suppresses T follicular helper cell differentiation and antibody responses
    Sala, Eleonora
    Nelli, Maria
    Laura, Chiara
    Di Lucia, Pietro
    Beccaria, Cristian Gabriel
    Bono, Elisa B.
    Mangione, Marta
    Marotta, Davide
    Sperto, Valentina
    Grillo, Marta
    Giustini, Leonardo
    Tosi, Fabio
    Nie, Jia
    Kim, Daehong
    Furiato, Giuliana
    Malpighi, Chiara
    Consolo, Eleonora
    Becher, Burkhard
    David, Eyal
    Cohen, Merav
    Giladi, Amir
    Amit, Ido
    Bosselut, Remy
    Guidotti, Luca G.
    Iannacone, Matteo
    Kuka, Mirela
    EMBO JOURNAL, 2025, : 2400 - 2423
  • [30] Immunosuppressive Property within the Streptococcus pneumoniae Cell Wall That Inhibits Generation of T Follicular Helper, Germinal Center, and Plasma Cell Response to a Coimmunized Heterologous Protein
    Saumyaa
    Arjunaraja, Swadhinya
    Pujanauski, Lindsey
    Colino, Jesus
    Torres, Raul M.
    Snapper, Clifford M.
    INFECTION AND IMMUNITY, 2013, 81 (09) : 3426 - 3433