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Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models
- Source :
- Blood. 124(11)
- Publication Year :
- 2014
-
Abstract
- Acute graft-versus-host disease (GVHD) is induced by alloreactivity of donor T cells toward host antigens presented on antigen-presenting cells (APCs). Apoptotic cells are capable of inducing tolerance by altering APC maturation. Apoptosis can be induced by extracorporeal photopheresis (ECP). We demonstrate that the use of ECP as a prophylaxis prior to conditioning significantly improves survival (P < .0001) after bone marrow transplantation (BMT) by inhibiting the initiation phase of acute GVHD in a murine BMT model. ECP-treated autologous splenocytes resulted in immune tolerance in the host, including reduced dendritic cell activation with decreased nuclear factor-κB engagement, increased regulatory T-cell (Treg) numbers with enhanced expression of cytolytic T lymphocyte-associated antigen 4, potentiating their suppressive function. The protective effect required host production of interleukin-10 and host Tregs. Conventional T cells that entered this tolerant environment experienced reduced proliferation, as well as a reduction of tissue homing and expression of activation markers. The induction of this tolerant state by ECP was obviated by cotreatment with lipopolysaccharide, suggesting that the inflammatory state of the recipient prior to treatment would play a role in potential clinical translation. The use of prophylactic ECP may provide an alternative and safe method for immunosuppression in the bone marrow transplant setting.
- Subjects :
- medicine.medical_treatment
Immunology
education
Antigen-Presenting Cells
Graft vs Host Disease
Apoptosis
Biochemistry
T-Lymphocytes, Regulatory
Immune tolerance
Mice
Mice, Inbred AKR
Antigen
immune system diseases
Inside BLOOD Commentary
Extracorporeal Photopheresis
medicine
Immune Tolerance
Animals
Antigen-presenting cell
Autografts
Bone Marrow Transplantation
Mice, Knockout
Mice, Inbred BALB C
business.industry
Immunosuppression
Cell Biology
Hematology
Dendritic cell
humanities
Interleukin-10
Transplantation
Interleukin 10
Disease Models, Animal
surgical procedures, operative
business
human activities
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 124
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....42627ed2d93e447053745a0454e3c2f1