Alloantigen presentation and graft-versus-host disease: fuel for the fire

Koyama, Motoko and Hill, Geoffrey R. (2016) Alloantigen presentation and graft-versus-host disease: fuel for the fire. Blood, 127 24: 2963-2970. doi:10.1182/blood-2016-02-697250

Author Koyama, Motoko
Hill, Geoffrey R.
Title Alloantigen presentation and graft-versus-host disease: fuel for the fire
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2016-06-16
Year available 2016
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1182/blood-2016-02-697250
Open Access Status Not yet assessed
Volume 127
Issue 24
Start page 2963
End page 2970
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
Allogeneic stem cell transplantation (SCT) is a unique procedure, primarily in patients with hematopoietic malignancies, involving chemoradiotherapy followed by the introduction of donor hematopoietic and immune cells into an inflamed and lymphopenic environment. Interruption of the process by which recipient alloantigen is presented to donor T cells to generate graft-versus-host disease (GVHD) represents an attractive therapeutic strategy to prevent morbidity and mortality after SCT and has been increasingly studied in the last 15 years. However, the immune activation resulting in GVHD has no physiological equivalent in nature; alloantigen is ubiquitous, persists indefinitely, and can be presented by multiple cell types at numerous sites, often on incompatible major histocompatibility complex, and occurs in the context of intense inflammation early after SCT. The recognition that alloantigen presentation is also critical to the development of immunological tolerance via both deletional and regulatory mechanisms further adds to this complexity. Finally, GVHD itself appears capable of inhibiting the presentation of microbiological antigens by donor dendritic cells late after SCT that is mandatory for the establishment of effective pathogen-specific immunity. Here, we review our current understanding of alloantigen, its presentation by various antigen-presenting cells, subsequent recognition by donor T cells, and the potential of therapeutic strategies interrupting this disease-initiating process to modify transplant outcome.
Keyword Bone marrow transplantation
Antigen presenting cells
Minor histocompatibility antigens
Plasmacytoid dendritic cells
Chronic myelogenous leukemia
Intestinal epithelial cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
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