Dendritic Cell Regulation of Graft-Vs.-Host Disease: Immunostimulation and Tolerance

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Feb 19

PMID 30774630

Citations 33

Authors

Hongshuang Yu

Yuanyuan Tian

Ying Wang

Shin Mineishi

Yi Zhang

Affiliations

Soon will be listed here.

Abstract

Graft-vs.-host disease (GVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Significant progresses have been made in defining the dichotomous role of dendritic cells (DCs) in the development of GVHD. Host-derived DCs are important to elicit allogeneic T cell responses, whereas certain donor-types of DCs derived from newly engrafted hematopoietic stem/progenitor cells (HSPCs) can amply this graft-vs.-host reaction. In contrast, some DCs also play non-redundant roles in mediating immune tolerance. They induce apoptotic deletion of host-reactive donor T cells while promoting expansion and function of regulatory T cells (Treg). Unfortunately, this tolerogenic effect of DCs is impaired during GVHD. Severe GVHD in patients subject to allo-HSCT is associated with significantly decreased number of circulating peripheral blood DCs during engraftment. Existing studies reveal that GVHD causes delayed reconstitution of donor DCs from engrafted HSPCs, impairs the antigen presentation function of newly generated DCs and reduces the capacity of DCs to regulate Treg. The present review will discuss the importance of DCs in alloimmunity and the mechanism underlying DC reconstitution after allo-HSCT.

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References

Jamieson B, Ahmed R . T cell memory. Long-term persistence of virus-specific cytotoxic T cells. J Exp Med. 1989; 169(6):1993-2005. PMC: 2189353. DOI: 10.1084/jem.169.6.1993. View

Choi S, Reddy P . Current and emerging strategies for the prevention of graft-versus-host disease. Nat Rev Clin Oncol. 2014; 11(9):536-47. PMC: 4151470. DOI: 10.1038/nrclinonc.2014.102. View

Boeckh M, Leisenring W, Riddell S, Bowden R, Huang M, Myerson D . Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood. 2002; 101(2):407-14. DOI: 10.1182/blood-2002-03-0993. View

Yamaguchi E, Chiba S, Kumano K, Kunisato A, Takahashi T, Takahashi T . Expression of Notch ligands, Jagged1, 2 and Delta1 in antigen presenting cells in mice. Immunol Lett. 2002; 81(1):59-64. DOI: 10.1016/s0165-2478(01)00326-1. View

Chung J, Ebens C, Perkey E, Radojcic V, Koch U, Scarpellino L . Fibroblastic niches prime T cell alloimmunity through Delta-like Notch ligands. J Clin Invest. 2017; 127(4):1574-1588. PMC: 5373885. DOI: 10.1172/JCI89535. View

Vander Lugt B, Khan A, Hackney J, Agrawal S, Lesch J, Zhou M . Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation. Nat Immunol. 2013; 15(2):161-7. DOI: 10.1038/ni.2795. View

Tamura H, Dong H, Zhu G, Sica G, Flies D, Tamada K . B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. Blood. 2001; 97(6):1809-16. DOI: 10.1182/blood.v97.6.1809. View

Kolb H, Schmid C, Barrett A, Schendel D . Graft-versus-leukemia reactions in allogeneic chimeras. Blood. 2003; 103(3):767-76. DOI: 10.1182/blood-2003-02-0342. View

Leveque-El Mouttie L, Koyama M, Le Texier L, Markey K, Cheong M, Kuns R . Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD. Blood. 2016; 128(6):794-804. PMC: 4982453. DOI: 10.1182/blood-2015-11-680876. View

10.

Teshima T, Reddy P, Lowler K, KuKuruga M, Liu C, Cooke K . Flt3 ligand therapy for recipients of allogeneic bone marrow transplants expands host CD8 alpha(+) dendritic cells and reduces experimental acute graft-versus-host disease. Blood. 2002; 99(5):1825-32. DOI: 10.1182/blood.v99.5.1825. View

11.

Weber M, Rudolph B, Stein P, Yogev N, Bosmann M, Schild H . Host-derived CD8⁺ dendritic cells protect against acute graft-versus-host disease after experimental allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 2014; 20(11):1696-704. DOI: 10.1016/j.bbmt.2014.08.005. View

12.

Highfill S, Rodriguez P, Zhou Q, Goetz C, Koehn B, Veenstra R . Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13. Blood. 2010; 116(25):5738-47. PMC: 3031417. DOI: 10.1182/blood-2010-06-287839. View

13.

Zeiser R, Blazar B . Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017; 377(22):2167-2179. PMC: 6034180. DOI: 10.1056/NEJMra1609337. View

14.

Ruutu T, Gratwohl A, de Witte T, Afanasyev B, Apperley J, Bacigalupo A . Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone Marrow Transplant. 2013; 49(2):168-73. DOI: 10.1038/bmt.2013.107. View

15.

Watowich S, Liu Y . Mechanisms regulating dendritic cell specification and development. Immunol Rev. 2010; 238(1):76-92. PMC: 3039024. DOI: 10.1111/j.1600-065X.2010.00949.x. View

16.

Markey K, Kuns R, Browne D, Gartlan K, Robb R, Martins J . Flt-3L Expansion of Recipient CD8α Dendritic Cells Deletes Alloreactive Donor T Cells and Represents an Alternative to Posttransplant Cyclophosphamide for the Prevention of GVHD. Clin Cancer Res. 2018; 24(7):1604-1616. DOI: 10.1158/1078-0432.CCR-17-2148. View

17.

Li H, Kaplan D, Matte-Martone C, Tan H, Venkatesan S, Johnson K . Langerhans cells are not required for graft-versus-host disease. Blood. 2010; 117(2):697-707. PMC: 3031488. DOI: 10.1182/blood-2010-07-299073. View

18.

Tawara I, Shlomchik W, Jones A, Zou W, Nieves E, Liu C . A crucial role for host APCs in the induction of donor CD4+CD25+ regulatory T cell-mediated suppression of experimental graft-versus-host disease. J Immunol. 2010; 185(7):3866-72. PMC: 2981818. DOI: 10.4049/jimmunol.1001625. View

19.

Ferrara J, Levine J, Reddy P, Holler E . Graft-versus-host disease. Lancet. 2009; 373(9674):1550-61. PMC: 2735047. DOI: 10.1016/S0140-6736(09)60237-3. View

20.

Zhang Y, Louboutin J, Zhu J, Rivera A, Emerson S . Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease. J Clin Invest. 2002; 109(10):1335-44. PMC: 150980. DOI: 10.1172/JCI14989. View