The Role of Co-stimulatory/Co-inhibitory Signals in Graft-vs.-Host Disease
Date
2018Journal
Frontiers in immunologyPublisher
Frontiers MediaType
Review
Metadata
Show full item recordAbstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapeutic approach for various hematologic and immunologic ailments. Despite the beneficial impact of allo-HCT, its adverse effects cause severe health concerns. After transplantation, recognition of host cells as foreign entities by donor T cells induces graft-vs.-host disease (GVHD). Activation, proliferation and trafficking of donor T cells to target organs and tissues are critical steps in the pathogenesis of GVHD. T cell activation is a synergistic process of T cell receptor (TCR) recognition of major histocompatibility complex (MHC)-anchored antigen and co-stimulatory/co-inhibitory signaling in the presence of cytokines. Most of the currently used therapeutic regimens for GVHD are based on inhibiting the allogeneic T cell response or T-cell depletion (TCD). However, the immunosuppressive drugs and TCD hamper the therapeutic potential of allo-HCT, resulting in attenuated graft-vs.-leukemia (GVL) effect as well as increased vulnerability to infection. In view of the drawback of overbroad immunosuppression, co-stimulatory, and co-inhibitory molecules are plausible targets for selective modulation of T cell activation and function that can improve the effectiveness of allo-HCT. Therefore, this review collates existing knowledge of T cell co-stimulation and co-inhibition with current research that may have the potential to provide novel approaches to cure GVHD without sacrificing the beneficial effects of allo-HCT.Keyword
allogeneic hematopoietic cell transplantation (allo-HCT)co-stimulation/co-inhibition
graft -vs.-leukemia (GVL) effect
graft-vs.-host disease (GVHD)
T cells
Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059796367&doi=10.3389%2ffimmu.2018.03003&partnerID=40&md5=87093651ec88983888110ad1aa5cfb2e; http://hdl.handle.net/10713/8904ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2018.03003
Scopus Count
Collections
Related articles
- Strategies for Enhancing and Preserving Anti-leukemia Effects Without Aggravating Graft-Versus-Host Disease.
- Authors: Chang YJ, Zhao XY, Huang XJ
- Issue date: 2018
- Daratumumab Prevents Experimental Xenogeneic Graft-Versus-Host Disease by Skewing Proportions of T Cell Functional Subsets and Inhibiting T Cell Activation and Migration.
- Authors: Gao Y, Shan W, Gu T, Zhang J, Wu Y, Li X, Zeng X, Zhou H, Chen Z, Xiao H
- Issue date: 2021
- Cytotoxic Pathways in Allogeneic Hematopoietic Cell Transplantation.
- Authors: Du W, Cao X
- Issue date: 2018
- Post-hematopoietic cell transplantation control of graft-versus-host disease by donor CD425 T cells to allow an effective graft-versus-leukemia response.
- Authors: Jones SC, Murphy GF, Korngold R
- Issue date: 2003 Apr