Skip to main content
SpringerLink
Log in

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

T cell activation is regulated by two distinct signals, signals one and two. Concanavalin A (ConA) is an antigen-independent mitogen and functions as signal one inducer, leading T cells to polyclonal proliferation. CD28 is known to be one of major costimulatory receptors and to provide signal two in the ConA-induced T cell proliferation. Here, we have studied the implication of other costimulatory pathways in the ConA-mediated T cell proliferation by using soluble recombinant proteins consisting of an extracellular domain of costimulatory receptors and Fc portion of human IgG. We found that T cell proliferation induced by ConA, but not PMA plus ionomycin or anti-CD3 mAb, is significantly inhibited by herpes virus entry mediator (HVEM)-Ig, even in the presence of CD28 signaling. Moreover, the high concentration of HVEM-Ig molecules almost completely suppressed ConA-mediated T cell proliferation. These results suggest that HVEM might play more important roles than CD28 in ConA-mediated T cell proliferation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.

Similar content being viewed by others

References

  • Abe R.; Vandenberghe P.; Craighead N.; Smoot D. S.; Lee K. P.; June C. H. Distinct signal transduction in mouse CD4+ and CD8+ splenic T cells after CD28 receptor ligation. J. Immunol. 154: 985–997; 1995.

    PubMed  CAS  Google Scholar 

  • Ahmann G. B.; Sachs D. H.; Hodes R. J. Requirement for an Ia-bearing accessory cell in Con A-induced T cell proliferation. J. Immunol. 121: 1981–1989; 1978.

    PubMed  CAS  Google Scholar 

  • Appleman L. J.; Berezovskaya A.; Grass I.; Boussiotis V. A. CD28 costimulation mediates T cell expansion via IL-2-independent and IL-2-dependent regulation of cell cycle progression. J. Immunol. 164: 144–151; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Bretscher P. A. A two-step, two-signal model for the primary activation of precursor helper T cells. Proc. Natl. Acad. Sci. U. S. A. 96: 185–190; 1999.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cai G.; Anumanthan A.; Brown J. A.; Greenfield E. A.; Zhu B.; Freeman G. J. CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator. Nat. Immunol. 9: 176–185; 2008.

    Article  PubMed  CAS  Google Scholar 

  • Cai G.; Freeman G. J. The CD160, BTLA. LIGHT/HVEM pathway: a bidirectional switch regulating T-cell activation. Immunol. Rev. 229: 244–258; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Chang C. P.; Yang M. C.; Liu H. S.; Lin Y. S.; Lei H. Y. Concanavalin A induces autophagy in hepatoma cells and has a therapeutic effect in a murine in situ hepatoma model. Hepatology 45: 286–296; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Chatila T. A.; Schwartz D. H.; Miller R.; Geha R. S. Requirement for mitogen, T cell-accessory cell contact, and interleukin 1 in the induction of resting T-cell proliferation. Clin. Immunol. Immunopathol. 44: 235–247; 1987.

    Article  PubMed  CAS  Google Scholar 

  • del Rio M. L.; Lucas C. L.; Buhler L.; Rayat G.; Rodriguez-Barbosa J. I. HVEM/LIGHT/BTLA/CD160 cosignaling pathways as targets for immune regulation. J. Leukoc. Biol. 87: 223–235; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Deppong C.; Degnan J. M.; Murphy T. L.; Murphy K. M.; Green J. M. B and T lymphocyte attenuator regulates T cell survival in the lung. J. Immunol. 181: 2973–2979; 2008.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Felipe I.; Bim S.; Somensi C. C. Increased clearance of Candida albicans from the peritoneal cavity of mice pretreated with concanavalin A or jacalin. Braz. J. Med. Biol. Res. 28: 477–483; 1995.

    PubMed  CAS  Google Scholar 

  • Harrop J. A.; McDonnell P. C.; Brigham-Burke M.; Lyn S. D.; Minton J.; Tan K. B.; Dede K.; Spampanato J.; Silverman C.; Hensley P.; DiPrinzio R.; Emery J. G.; Deen K.; Eichman C.; Chabot-Fletcher M.; Truneh A.; Young P. R. Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth. J. Biol. Chem. 273: 27548–27556; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Kanaya K.; Tsuchida Y.; Inobe M.; Murakami M.; Hirose T.; Kon S.; Kawaguchi S.; Wada T.; Yamashita T.; Ishii S.; Uede T. Combined gene therapy with adenovirus vectors containing CTLA4Ig and CD40Ig prolongs survival of composite tissue allografts in rat model. Transplantation 75: 275–281; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Kaneko Y.; Harada M.; Kawano T.; Yamashita M.; Shibata Y.; Gejyo F.; Nakayama T.; Taniguchi M. Augmentation of Valpha14 NKT cell-mediated cytotoxicity by interleukin 4 in an autocrine mechanism resulting in the development of concanavalin A-induced hepatitis. J. Exp. Med. 191: 105–114; 2000.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kaposzta R.; Tree P.; Marodi L.; Gordon S. Characteristics of invasive candidiasis in gamma interferon- and interleukin-4-deficient mice: role of macrophages in host defense against Candida albicans. Infect. Immun. 66: 1708–1717; 1998.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Khoruts A.; Mondino A.; Pape K. A.; Reiner S. L.; Jenkins M. K. A natural immunological adjuvant enhances T cell clonal expansion through a CD28-dependent, interleukin (IL)-2-independent mechanism. J. Exp. Med. 187: 225–236; 1998.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lei H. Y.; Chang C. P. Lectin of Concanavalin A as an anti-hepatoma therapeutic agent. J. Biomed. Sci. 16: 10; 2009.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Leo O.; Foo M.; Sachs D. H.; Samelson L. E.; Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc. Natl. Acad. Sci. U. S. A. 84: 1374–1378; 1987.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ma D. Y.; Clark E. A. The role of CD40 and CD154/CD40L in dendritic cells. Semin. Immunol. 21: 265–272; 2009.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Matsui Y.; Okamoto H.; Inobe M.; Jia N.; Shimizu T.; Akino M.; Sugawara T.; Tezuka K.; Nakayama Y.; Morimoto J.; Kimura C.; Kon S.; Miyazaki T.; Kitabatake A.; Uede T. Adenovirus-mediated gene transfer of ICOSIg fusion protein ameliorates ongoing experimental autoimmune myocarditis. Hum. Gene Ther. 14: 521–532; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Mauri D. N.; Ebner R.; Montgomery R. I.; Kochel K. D.; Cheung T. C.; Yu G. L.; Ruben S.; Murphy M.; Eisenberg R. J.; Cohen G. H.; Spear P. G.; Ware C. F. LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator. Immunity 8: 21–30; 1998.

    Article  PubMed  CAS  Google Scholar 

  • McAdam A. J.; Chang T. T.; Lumelsky A. E.; Greenfield E. A.; Boussiotis V. A.; Duke-Cohan J. S.; Chernova T.; Malenkovich N.; Jabs C.; Kuchroo V. K.; Ling V.; Collins M.; Sharpe A. H.; Freeman G. J. Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells. J. Immunol. 165: 5035–5040; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Miyagi T.; Takehara T.; Tatsumi T.; Suzuki T.; Jinushi M.; Kanazawa Y.; Hiramatsu N.; Kanto T.; Tsuji S.; Hori M.; Hayashi N. Concanavalin a injection activates intrahepatic innate immune cells to provoke an antitumor effect in murine liver. Hepatology 40: 1190–1196; 2004.

    Article  PubMed  CAS  Google Scholar 

  • Morel Y.; Truneh A.; Sweet R. W.; Olive D.; Costello R. T. The TNF superfamily members LIGHT and CD154 (CD40 Ligand) costimulate induction of dendritic cell maturation and elicit specific CTL activity. J. Immunol. 167: 2479–2486; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Ono E.; Yoshino S.; Amagai K.; Taharaguchi S.; Kimura C.; Morimoto J.; Inobe M.; Uenishi T.; Uede T. Enhanced resistance to herpes simplex virus type 1 infection in transgenic mice expressing a soluble form of herpesvirus entry mediator. Virology 320: 267–275; 2004.

    Article  PubMed  CAS  Google Scholar 

  • Perrin P. J.; Davis T. A.; Smoot D. S.; Abe R.; June C. H.; Lee K. P. Mitogenic stimulation of T cells reveals differing contributions for B7-1 (CD80) and B7-2 (CD86) costimulation. Immunology 90: 534–542; 1997.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rothstein D. M.; Sayegh M. H. T-cell costimulatory pathways in allograft rejection and tolerance. Immunol. Rev. 196: 85–108; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Rudd C. E.; Taylor A.; Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol. Rev. 229: 12–26; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Salomon B.; Bluestone J. A. Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu. Rev. Immunol. 19: 225–252; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Sedy J. R.; Gavrieli M.; Potter K. G.; Hurchla M. A.; Lindsley R. C.; Hildner K.; Scheu S.; Pfeffer K.; Ware C. F.; Murphy T. L.; Murphy K. M. B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat. Immunol. 6: 90–98; 2005.

    Article  PubMed  CAS  Google Scholar 

  • Shahinian A.; Pfeffer K.; Lee K. P.; Kundig T. M.; Kishihara K.; Wakeham A.; Kawai K.; Ohashi P. S.; Thompson C. B.; Mak T. W. Differential T cell costimulatory requirements in CD28-deficient mice. Science 261: 609–612; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Simpson T. R.; Quezada S. A.; Allison J. P. Regulation of CD4 T cell activation and effector function by inducible costimulator (ICOS). Curr. Opin. Immunol. 22: 326–332; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Sinclair N. R. Why so many coinhibitory receptors? Scand. J. Immunol. 50: 10–13; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Tamada K.; Shimozaki K.; Chapoval A. I.; Zhai Y.; Su J.; Chen S. F.; Hsieh S. L.; Nagata S.; Ni J.; Chen L. LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response. J. Immunol. 164: 4105–4110; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Tiegs G.; Hentschel J.; Wendel A. A T cell-dependent experimental liver injury in mice inducible by concanavalin A. J. Clin. Invest. 90: 196–203; 1992.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Toyabe S.; Seki S.; Iiai T.; Takeda K.; Shirai K.; Watanabe H.; Hiraide H.; Uchiyama M.; Abo T. Requirement of IL-4 and liver NK1+ T cells for concanavalin A-induced hepatic injury in mice. J. Immunol. 159: 1537–1542; 1997.

    PubMed  CAS  Google Scholar 

  • Wallach D.; Varfolomeev E. E.; Malinin N. L.; Goltsev Y. V.; Kovalenko A. V.; Boldin M. P. Tumor necrosis factor receptor and Fas signaling mechanisms. Annu. Rev. Immunol. 17: 331–367; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Walunas T. L.; Lenschow D. J.; Bakker C. Y.; Linsley P. S.; Freeman G. J.; Green J. M.; Thompson C. B.; Bluestone J. A. CTLA-4 can function as a negative regulator of T cell activation. Immunity 1: 405–413; 1994.

    Article  PubMed  CAS  Google Scholar 

  • Weiss A.; Shields R.; Newton M.; Manger B.; Imboden J. Ligand-receptor interactions required for commitment to the activation of the interleukin 2 gene. J. Immunol. 138: 2169–2176; 1987.

    PubMed  CAS  Google Scholar 

  • Yang M. C.; Chang C. P.; Lei H. Y. Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis. Int. Immunol. 22: 661–670; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Yokoyama Y. M.; Koning F.; Kehn P. J.; Pereira G. M. B.; Stingl G.; Coligan J. E.; Shevach E. M. Characterization of a cell surface-expressed disulfide-linked dimer involved in murine T cell activation. J. Immunol. 141: 369–376; 1988.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Chiemi Kimura and Hisako Yata for the preparation of Ig-fusion molecules. This study was partly supported by the Takeda foundation.

Author information

Authors and Affiliations

  1. Laboratory of Human Molecular Genetics, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan

    Yoshiaki Ando, Chika Yasuoka, Takuya Mishima, Takuya Ikematsu, Tsukasa Matsunaga & Manabu Inobe

  2. Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo, 060-0815, Japan

    Toshimitsu Uede

Authors
  1. Yoshiaki Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chika Yasuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takuya Mishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takuya Ikematsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toshimitsu Uede
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tsukasa Matsunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manabu Inobe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manabu Inobe.

Additional information

Editor: T. Okamoto

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ando, Y., Yasuoka, C., Mishima, T. et al. Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule. In Vitro Cell.Dev.Biol.-Animal 50, 313–320 (2014). https://doi.org/10.1007/s11626-013-9705-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-013-9705-2

Keywords

Search

Navigation