Evidence for Contribution of CD4+ CD25+ Regulatory T Cells in Maintaining Immune Tolerance to Human Factor IX Following Perinatal Adenovirus Vector Delivery

Overview

Journal J Immunol Res

Publisher Wiley

Specialty Allergy & Immunology

Date 2015 Mar 12

PMID 25759840

Citations 6

Authors

Megha S Nivsarkar

Suzanne M K Buckley

Alan L Parker

Dany Perocheau

Tristan R McKay

Ahad A Rahim

Steven J Howe

Simon N Waddington

Affiliations

Soon will be listed here.

Abstract

Following fetal or neonatal gene transfer in mice and other species immune tolerance of the transgenic protein is frequently observed; however the underlying mechanisms remain largely undefined. In this study fetal and neonatal BALB/c mice received adenovirus vector to deliver human factor IX (hFIX) cDNA. The long-term tolerance of hFIX was robust in the face of immune challenge with hFIX protein and adjuvant but was eliminated by simultaneous administration of anti-CD25+ antibody. Naive irradiated BALB/c mice which had received lymphocytes from donors immunised with hFIX developed anti-hFIX antibodies upon immune challenge. Cotransplantation with CD4+CD25+ cells isolated from neonatally tolerized donors decreased the antibody response. In contrast, cotransplantation with CD4+CD25- cells isolated from the same donors increased the antibody response. These data provide evidence that immune tolerance following perinatal gene transfer is maintained by a CD4+CD25+ regulatory population.

Citing Articles

Fetal gene therapy.

Waddington S, Peranteau W, Rahim A, Boyle A, Kurian M, Gissen P J Inherit Metab Dis. 2023; 47(1):192-210.

PMID: 37470194 PMC: 10799196. DOI: 10.1002/jimd.12659.

Production of lentiviral vectors using novel, enzymatically produced, linear DNA.

Karda R, Counsell J, Karbowniczek K, Caproni L, Tite J, Waddington S Gene Ther. 2019; 26(3-4):86-92.

PMID: 30643205 PMC: 6760675. DOI: 10.1038/s41434-018-0056-1.

Fetal gene therapy for neurodegenerative disease of infants.

Massaro G, Mattar C, Wong A, Sirka E, Buckley S, Herbert B Nat Med. 2018; 24(9):1317-1323.

PMID: 30013199 PMC: 6130799. DOI: 10.1038/s41591-018-0106-7.

Neonatal Gene Therapy for Hemophilia B by a Novel Adenovirus Vector Showing Reduced Leaky Expression of Viral Genes.

Iizuka S, Sakurai F, Tachibana M, Ohashi K, Mizuguchi H Mol Ther Methods Clin Dev. 2017; 6:183-193.

PMID: 28828393 PMC: 5552065. DOI: 10.1016/j.omtm.2017.07.001.

A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice.

Yang Y, Wang L, Bell P, McMenamin D, He Z, White J Nat Biotechnol. 2016; 34(3):334-8.

PMID: 26829317 PMC: 4786489. DOI: 10.1038/nbt.3469.

References

Buckley S, Howe S, Rahim A, Buning H, McIntosh J, Wong S . Luciferin detection after intranasal vector delivery is improved by intranasal rather than intraperitoneal luciferin administration. Hum Gene Ther. 2008; 19(10):1050-6. DOI: 10.1089/hum.2008.023. View

Chandler R, Venditti C . Adenovirus-mediated gene delivery rescues a neonatal lethal murine model of mut(0) methylmalonic acidemia. Hum Gene Ther. 2007; 19(1):53-60. PMC: 2683146. DOI: 10.1089/hum.2007.0118. View

Mold J, Venkatasubrahmanyam S, Burt T, Michaelsson J, Rivera J, Galkina S . Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans. Science. 2010; 330(6011):1695-9. PMC: 3276679. DOI: 10.1126/science.1196509. View

Ward N, Buckley S, Waddington S, VandenDriessche T, Chuah M, Nathwani A . Codon optimization of human factor VIII cDNAs leads to high-level expression. Blood. 2010; 117(3):798-807. DOI: 10.1182/blood-2010-05-282707. View

Rahim A, Wong A, Hoefer K, Buckley S, Mattar C, Cheng S . Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of CNS cell types and extensive transduction of the nervous system. FASEB J. 2011; 25(10):3505-18. DOI: 10.1096/fj.11-182311. View

Mold J, McCune J . Immunological tolerance during fetal development: from mouse to man. Adv Immunol. 2012; 115:73-111. DOI: 10.1016/B978-0-12-394299-9.00003-5. View

Shi Y, Falahati R, Zhang J, Flebbe-Rehwaldt L, Gaensler K . Role of antigen-specific regulatory CD4+CD25+ T cells in tolerance induction after neonatal IP administration of AAV-hF.IX. Gene Ther. 2013; 20(10):987-96. PMC: 3795474. DOI: 10.1038/gt.2013.22. View

Carlon M, Vidovic D, Dooley J, da Cunha M, Maris M, Lampi Y . Immunological ignorance allows long-term gene expression after perinatal recombinant adeno-associated virus-mediated gene transfer to murine airways. Hum Gene Ther. 2014; 25(6):517-28. PMC: 4064737. DOI: 10.1089/hum.2013.196. View

Holladay S, Smialowicz R . Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure. Environ Health Perspect. 2000; 108 Suppl 3:463-73. PMC: 1637831. DOI: 10.1289/ehp.00108s3463. View

10.

Colin M, Moritz S, Schneider H, Capeau J, Coutelle C, Brahimi-Horn M . Haemoglobin interferes with the ex vivo luciferase luminescence assay: consequence for detection of luciferase reporter gene expression in vivo. Gene Ther. 2000; 7(15):1333-6. DOI: 10.1038/sj.gt.3301248. View

11.

Tran N, Porada C, Almeida-Porada G, GLIMP H, Anderson W, Zanjani E . Induction of stable prenatal tolerance to beta-galactosidase by in utero gene transfer into preimmune sheep fetuses. Blood. 2001; 97(11):3417-23. DOI: 10.1182/blood.v97.11.3417. View

12.

Hayashi S, Peranteau W, Shaaban A, Flake A . Complete allogeneic hematopoietic chimerism achieved by a combined strategy of in utero hematopoietic stem cell transplantation and postnatal donor lymphocyte infusion. Blood. 2002; 100(3):804-12. DOI: 10.1182/blood-2002-01-0016. View

13.

Waddington S, Buckley S, Nivsarkar M, Jezzard S, Schneider H, Dahse T . In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor. Blood. 2002; 101(4):1359-66. DOI: 10.1182/blood-2002-03-0779. View

14.

Zhang F, Liang Z, Matsuki N, Van Kaer L, Joyce S, Wakeland E . A murine locus on chromosome 18 controls NKT cell homeostasis and Th cell differentiation. J Immunol. 2003; 171(9):4613-20. DOI: 10.4049/jimmunol.171.9.4613. View

15.

Zhang J, Xu L, Haskins M, Ponder K . Neonatal gene transfer with a retroviral vector results in tolerance to human factor IX in mice and dogs. Blood. 2003; 103(1):143-51. DOI: 10.1182/blood-2003-06-2181. View

16.

Waddington S, Nivsarkar M, Mistry A, Buckley S, Kemball-Cook G, Mosley K . Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy. Blood. 2004; 104(9):2714-21. DOI: 10.1182/blood-2004-02-0627. View

17.

Waddington S, Kramer M, Hernandez-Alcoceba R, Buckley S, Themis M, Coutelle C . In utero gene therapy: current challenges and perspectives. Mol Ther. 2005; 11(5):661-76. DOI: 10.1016/j.ymthe.2005.01.015. View

18.

Stills Jr H . Adjuvants and antibody production: dispelling the myths associated with Freund's complete and other adjuvants. ILAR J. 2005; 46(3):280-93. DOI: 10.1093/ilar.46.3.280. View

19.

Xu L, Mei M, Haskins M, Nichols T, ODonnell P, Cullen K . Immune response after neonatal transfer of a human factor IX-expressing retroviral vector in dogs, cats, and mice. Thromb Res. 2006; 120(2):269-80. DOI: 10.1016/j.thromres.2006.09.010. View

20.

Cao O, Dobrzynski E, Wang L, Nayak S, Mingle B, Terhorst C . Induction and role of regulatory CD4+CD25+ T cells in tolerance to the transgene product following hepatic in vivo gene transfer. Blood. 2007; 110(4):1132-40. PMC: 1939896. DOI: 10.1182/blood-2007-02-073304. View