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Keratinocyte Growth Factor Improves Allogeneic Bone Marrow Engraftment through a CD4(+)Foxp3(+) Regulatory T Cell-Dependent Mechanism
- Source :
- Journal of Immunology, 182(12), 7364-7369. American Association of Immunologists
- Publication Year :
- 2009
-
Abstract
- Keratinocyte growth factor (KGF) protects mice from acute graft-vs-host disease and graft rejection by cytoprotective and yet incompletely understood immunological mechanisms. Recently, we showed that administration of KGF induces selective peripheral expansion of CD4(+)Foxp3(+) regulatory T cells (Treg). In this study, we set out to assess whether the peripheral expansion of Treg accounts for the immunomodulatory effects of KGF after bone marrow (BM) transplantation. To exclude potentially confounding cytoprotective and thymopoietic effects of KGF, we applied KGF to congenic wild-type mice that served as T cell provider mice for T and B cell-deficient RAG-1(-/-) mice that were subsequently transplanted with allogeneic BM. Treatment of congenic T cell provider mice with KGF significantly improved engraftment and reduced graft rejection in BMT recipients. CD4(+)Foxp3(+) Treg remained increased for 4 wk, while expansion of congenic CD3(+) T cells was inhibited. To assess a causal relationship between expansion of Treg and improved BM engraftment, congenic Scurfy mice, which lack Foxp3(+) Treg, served as T cell provider mice and were treated with KGF. KGF-treatment of Scurfy mice did not affect engraftment nor did it inhibit the expansion of congenic T cells. These data demonstrate that administration of KGF to the T cell provider mice improves engraftment of allogeneic BM through a CD4(+)Foxp3(+) Treg-dependent mechanism. The Journal of Immunology, 2009, 182: 7364-7369.
- Subjects :
- Fibroblast Growth Factor 7
Regulatory T cell
T cell
CD3
Immunology
Congenic
chemical and pharmacologic phenomena
T-Lymphocytes, Regulatory
chemistry.chemical_compound
Mice
Th2 Cells
Bone Marrow
medicine
Immunology and Allergy
Animals
Transplantation, Homologous
Bone Marrow Transplantation
Cell Proliferation
Mice, Knockout
biology
business.industry
Graft Survival
FOXP3
Forkhead Transcription Factors
hemic and immune systems
Th1 Cells
Transplantation
medicine.anatomical_structure
chemistry
biology.protein
Bone marrow
Keratinocyte growth factor
business
Subjects
Details
- ISSN :
- 00221767
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology, 182(12), 7364-7369. American Association of Immunologists
- Accession number :
- edsair.doi.dedup.....52d3ff3c987061a4e7cd77d5be0fe067