The Role of Co-stimulatory/Co-inhibitory Signals in Graft-vs.-Host Disease
Kumar, Sandeep ; Leigh, Nicholas D LU
and Cao, Xuefang
(2018)
In Frontiers in Immunology
9.
- Abstract
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... (More)
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.
(Less)
- author
- Kumar, Sandeep
; Leigh, Nicholas D
LU
and Cao, Xuefang
- publishing date
- 2018-12-21
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Clinical Trials as Topic, Costimulatory and Inhibitory T-Cell Receptors/agonists, Graft vs Host Disease/immunology, Graft vs Leukemia Effect/drug effects, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Immunologic Factors/pharmacology, Immunotherapy/methods, Major Histocompatibility Complex/immunology, Signal Transduction/drug effects, T-Lymphocytes/drug effects, Transplantation, Homologous/adverse effects, Treatment Outcome
- in
- Frontiers in Immunology
- volume
- 9
- article number
- 3003
- publisher
- Frontiers Media S. A.
- external identifiers
-
- pmid:30627129
- scopus:85059796367
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2018.03003
- language
- English
- LU publication?
- no
- id
- 43ae7865-51cf-4859-a524-3d9cc9490796
- date added to LUP
- 2020-04-27 21:00:22
- date last changed
- 2024-04-03 06:41:37
@article{43ae7865-51cf-4859-a524-3d9cc9490796,
abstract = {{<p>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.</p>}},
author = {{Kumar, Sandeep and Leigh, Nicholas D and Cao, Xuefang}},
issn = {{1664-3224}},
keywords = {{Clinical Trials as Topic; Costimulatory and Inhibitory T-Cell Receptors/agonists; Graft vs Host Disease/immunology; Graft vs Leukemia Effect/drug effects; Hematopoietic Stem Cell Transplantation/adverse effects; Humans; Immunologic Factors/pharmacology; Immunotherapy/methods; Major Histocompatibility Complex/immunology; Signal Transduction/drug effects; T-Lymphocytes/drug effects; Transplantation, Homologous/adverse effects; Treatment Outcome}},
language = {{eng}},
month = {{12}},
publisher = {{Frontiers Media S. A.}},
series = {{Frontiers in Immunology}},
title = {{The Role of Co-stimulatory/Co-inhibitory Signals in Graft-vs.-Host Disease}},
url = {{http://dx.doi.org/10.3389/fimmu.2018.03003}},
doi = {{10.3389/fimmu.2018.03003}},
volume = {{9}},
year = {{2018}},
}