Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism - PubMed

Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism

David C Gondek et al. J Immunol. 2005.

Abstract

CD4+CD25+ regulatory T cells (Treg) are potent immunosuppressive cells that are pivotal in the regulation of peripheral tolerance. In this report, we identify granzyme B (GZ-B) as one of the key components of Treg-mediated suppression. Induction of regulatory activity is correlated with the up-regulation of GZ-B expression. Proof of a functional involvement of GZ-B in contact-mediated suppression by Treg is shown by the reduced ability of Treg from GZ-B-/- mice to suppress as efficiently as Treg from WT mice. GZ-B-mediated suppression is perforin independent, because suppression by Treg from perforin-/- and WT is indistinguishable. Additionally, suppression mediated by Treg appears to be mediated, in part, by the induction of apoptosis in the CD4+CD25- effector cell. In summary, GZ-B is one of the key mechanisms through which CD4+CD25+ Treg induce cell contact-mediated suppression.

Similar articles

• Reciprocal granzyme/perforin-mediated death of human regulatory and responder T cells is regulated by interleukin-2 (IL-2).

  Czystowska M, Strauss L, Bergmann C, Szajnik M, Rabinowich H, Whiteside TL. Czystowska M, et al. J Mol Med (Berl). 2010 Jun;88(6):577-88. doi: 10.1007/s00109-010-0602-9. Epub 2010 Mar 12. J Mol Med (Berl). 2010. PMID: 20225066 Free PMC article.

• Double-negative T cells, activated by xenoantigen, lyse autologous B and T cells using a perforin/granzyme-dependent, Fas-Fas ligand-independent pathway.

  Zhang ZX, Ma Y, Wang H, Arp J, Jiang J, Huang X, He KM, Garcia B, Madrenas J, Zhong R. Zhang ZX, et al. J Immunol. 2006 Nov 15;177(10):6920-9. doi: 10.4049/jimmunol.177.10.6920. J Immunol. 2006. PMID: 17082607

• A novel mechanism of regulatory T cell-mediated down-regulation of autoimmunity.

  Qin HY, Mukherjee R, Lee-Chan E, Ewen C, Bleackley RC, Singh B. Qin HY, et al. Int Immunol. 2006 Jul;18(7):1001-15. doi: 10.1093/intimm/dxl035. Epub 2006 May 4. Int Immunol. 2006. PMID: 16675487

• Perforin-dependent nuclear targeting of granzymes: A central role in the nuclear events of granule-exocytosis-mediated apoptosis?

  Blink EJ, Trapani JA, Jans DA. Blink EJ, et al. Immunol Cell Biol. 1999 Jun;77(3):206-15. doi: 10.1046/j.1440-1711.1999.00817.x. Immunol Cell Biol. 1999. PMID: 10361252 Review.

• The orphan granzymes of humans and mice.

  Grossman WJ, Revell PA, Lu ZH, Johnson H, Bredemeyer AJ, Ley TJ. Grossman WJ, et al. Curr Opin Immunol. 2003 Oct;15(5):544-52. doi: 10.1016/s0952-7915(03)00099-2. Curr Opin Immunol. 2003. PMID: 14499263 Review.

Cited by

• OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential.

  Lai C, August S, Albibas A, Behar R, Cho SY, Polak ME, Theaker J, MacLeod AS, French RR, Glennie MJ, Al-Shamkhani A, Healy E. Lai C, et al. Clin Cancer Res. 2016 Aug 15;22(16):4236-48. doi: 10.1158/1078-0432.CCR-15-2614. Epub 2016 Mar 31. Clin Cancer Res. 2016. PMID: 27034329 Free PMC article.

• Tumor microenvironment in pancreatic ductal adenocarcinoma: Implications in immunotherapy.

  Smith C, Zheng W, Dong J, Wang Y, Lai J, Liu X, Yin F. Smith C, et al. World J Gastroenterol. 2022 Jul 21;28(27):3297-3313. doi: 10.3748/wjg.v28.i27.3297. World J Gastroenterol. 2022. PMID: 36158269 Free PMC article. Review.

• The potential of autologous regulatory T cell (Treg) therapy to prevent Cardiac Allograft Vasculopathy (CAV) in paediatric heart transplant recipients.

  Aiyengar A, Romano M, Burch M, Lombardi G, Fanelli G. Aiyengar A, et al. Front Immunol. 2024 Sep 9;15:1444924. doi: 10.3389/fimmu.2024.1444924. eCollection 2024. Front Immunol. 2024. PMID: 39315099 Free PMC article. Review.

• Integrins in Health and Disease-Suitable Targets for Treatment?

  Klaus T, Hieber C, Bros M, Grabbe S. Klaus T, et al. Cells. 2024 Jan 23;13(3):212. doi: 10.3390/cells13030212. Cells. 2024. PMID: 38334604 Free PMC article. Review.

• Genetic deletion of granzyme B does not confer resistance to the development of spontaneous diabetes in non-obese diabetic mice.

  Kobayashi M, Kaneko-Koike C, Abiru N, Uchida T, Akazawa S, Nakamura K, Kuriya G, Satoh T, Ida H, Kawasaki E, Yamasaki H, Nagayama Y, Sasaki H, Kawakami A. Kobayashi M, et al. Clin Exp Immunol. 2013 Sep;173(3):411-8. doi: 10.1111/cei.12134. Clin Exp Immunol. 2013. PMID: 23663075 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Silverchair Information Systems

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • SciCrunch