publication . Article . 2018

Donor-Derived Regulatory Dendritic Cell Infusion Maintains Donor-Reactive CD4+CTLA4hi T Cells in Non-Human Primate Renal Allograft Recipients Treated with CD28 Co-Stimulation Blockade.

Mohamed B. Ezzelarab; Lien Lu; William F. Shufesky; Adrian E. Morelli; Adrian E. Morelli; Angus W. Thomson; Angus W. Thomson;
Open Access
  • Published: 01 Feb 2018 Journal: Frontiers in Immunology, volume 9 (eissn: 1664-3224, Copyright policy)
  • Publisher: Frontiers Media SA
Abstract
Donor-derived regulatory dendritic cell (DCreg) infusion before transplantation, significantly prolongs renal allograft survival in non-human primates. This is associated with enhanced expression of the immunoregulatory molecules cytotoxic T-lymphocyte-associated antigen (Ag) 4 (CTLA4) and programmed cell death protein 1 (PD1) by host donor-reactive T cells. In rodents and humans, CD28 co-stimulatory pathway blockade with the fusion protein CTLA4:Ig (CTLA4Ig) is associated with reduced differentiation and development of regulatory T cells (Treg). We hypothesized that upregulation of CTLA4 by donor-reactive CD4+ T cells in DCreg-infused recipients treated with CT...
Subjects
free text keywords: Immunology, Original Research, regulatory T cells, dendritic cells, co-stimulation blockade, renal allografts, non-human primates, Immunologic diseases. Allergy, RC581-607, Chemistry, Transplantation, Endocrinology, medicine.medical_specialty, medicine, T cell, medicine.anatomical_structure, Internal medicine, Antigen, Blockade, Downregulation and upregulation, Dendritic cell, CD28, Cytotoxic T cell
Funded by
NIH| Rhesus Monkey Dendritic Cells for Transplant Tolerance
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2U01AI051698-06
  • Funding stream: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
58 references, page 1 of 4

1 Lechler RI Sykes M Thomson AW Turka LA Organ transplantation—how much of the promise has been realized?Nat Med (2005) 11:605–13.10.1038/nm1251 15937473 [OpenAIRE] [PubMed] [DOI]

2 Bluestone JA Thomson AW Shevach EM Weiner HL. What does the future hold for cell-based tolerogenic therapy?Nat Rev Immunol (2007) 7:650–4.10.1038/nri2137 17653127 [OpenAIRE] [PubMed] [DOI]

3 Morelli AE Thomson AW. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol (2007) 7:610–21.10.1038/nri2132 17627284 [OpenAIRE] [PubMed] [DOI]

4 Lombardi G Sagoo P Scotta C Fazekasova H Smyth L Tsang J Cell therapy to promote transplantation tolerance: a winning strategy?Immunotherapy (2011) 3:28–31.10.2217/imt.11.42 21524166 [OpenAIRE] [PubMed] [DOI]

5 Wood KJ Bushell A Hester J. Regulatory immune cells in transplantation. Nat Rev Immunol (2012) 12:417–30.10.1038/nri3227 22627860 [OpenAIRE] [PubMed] [DOI]

6 Steptoe RJ Thomson AW. Dendritic cells and tolerance induction. Clin Exp Immunol (1996) 105:397–402.10.1046/j.1365-2249.1996.d01-779.x 8809125 [OpenAIRE] [PubMed] [DOI]

7 Steinman RM Hawiger D Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol (2003) 21:685–711.10.1146/annurev.immunol.21.120601.141040 12615891 [OpenAIRE] [PubMed] [DOI]

8 Stenger EO Turnquist HR Mapara MY Thomson AW. Dendritic cells and regulation of graft-versus-host disease and graft-versus-leukemia activity. Blood (2012) 119:5088–103.10.1182/blood-2011-11-364091 22403259 [OpenAIRE] [PubMed] [DOI]

9 Nasreen M Waldie TM Dixon CM Steptoe RJ. Steady-state antigen-expressing dendritic cells terminate CD4+ memory T-cell responses. Eur J Immunol (2010) 40:2016–25.10.1002/eji.200940085 20405475 [OpenAIRE] [PubMed] [DOI]

10 Anderson AE Sayers BL Haniffa MA Swan DJ Diboll J Wang XN Differential regulation of naive and memory CD4+ T cells by alternatively activated dendritic cells. J Leukoc Biol (2008) 84:124–33.10.1189/jlb.1107744 18430785 [OpenAIRE] [PubMed] [DOI]

11 Kenna TJ Waldie T McNally A Thomson M Yagita H Thomas R Targeting antigen to diverse APCs inactivates memory CD8+ T cells without eliciting tissue-destructive effector function. J Immunol (2010) 184:598–606.10.4049/jimmunol.0900032 19995901 [OpenAIRE] [PubMed] [DOI]

12 Valujskikh A. The challenge of inhibiting alloreactive T-cell memory. Am J Transplant (2006) 6:647–51.10.1111/j.1600-6143.2005.01215.x 16539619 [OpenAIRE] [PubMed] [DOI]

13 Valujskikh A Lakkis FG. In remembrance of things past: memory T cells and transplant rejection. Immunol Rev (2003) 196:65–74.10.1046/j.1600-065X.2003.00087.x 14617198 [OpenAIRE] [PubMed] [DOI]

14 Lakkis FG Sayegh MH Memory T cells: a hurdle to immunologic tolerance. J Am Soc Nephrol (2003) 14:2402–10.10.1097/01.ASN.0000085020.78117.70 12937320 [OpenAIRE] [PubMed] [DOI]

15 Ford ML Larsen CP. Overcoming the memory barrier in tolerance induction: molecular m imicry and functional heterogeneity among pathogen-specific T-cell populations. Curr Opin Organ Transplant (2010) 15:405–10.10.1097/MOT.0b013e32833b7916 20616729 [OpenAIRE] [PubMed] [DOI]

58 references, page 1 of 4
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