Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease

Autor: Osamu Ohara, Takashi Saito, Sho Yamasaki, Atsushi Hijikata, Kawori Eizumi, Hideaki Takagi, Naohide Yamashita, Kaori Sato, Yumiko Sato, Katsuaki Sato, Shigeharu Fujita, Hiroshi Kitamura, Mai Yamamoto, Tomohiro Fukaya
Rok vydání: 2009
Předmět:
medicine.medical_treatment
Immunology
Graft vs Host Disease
Enzyme-Linked Immunosorbent Assay
Mice
Transgenic
Hematopoietic stem cell transplantation
Major histocompatibility complex
Skin Diseases
T-Lymphocytes
Regulatory
Biochemistry
Mice
Bone Marrow
T-Lymphocyte Subsets
Leukocytes
Minor histocompatibility antigen
medicine
Animals
Transplantation
Homologous
RNA
Messenger
Antigen-presenting cell
Bone Marrow Transplantation
Mice
Knockout
Mice
Inbred BALB C
Membrane Glycoproteins
biology
Reverse Transcriptase Polymerase Chain Reaction
Hematopoietic Stem Cell Transplantation
Dendritic Cells
Cell Biology
Hematology
Dendritic cell
Flow Cytometry
medicine.disease
DNA-Binding Proteins
Mice
Inbred C57BL
Retroviridae
medicine.anatomical_structure
Graft-versus-host disease
Chronic Disease
biology.protein
Transplantation Tolerance
Bone marrow
Stem cell
Zdroj: Blood. 113:4780-4789
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood-2008-10-183145
Popis: Chronic graft-versus-host disease (cGVHD) is a limiting factor in allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of leukemia and other malignancies. Relative to the process that initiates and promotes cGVHD, the regulation is poorly understood. In this study, we examined the role of naturally occurring regulatory dendritic cells (DCregs) in murine major histocompatibility complex (MHC)-compatible and multiple minor histocompatibility antigen (miHAg)–incompatible model of cGVHD in alloHSCT. DCregs generated from bone marrow in vitro (BM-DCregs) exclusively expressed CD200 receptor 3 (CD200R3), which exerted a suppressive function in the Ag-specific CD4+ T-cell response. CD49+CD200R3+ cells showed similarities in phenotype and function to BM-DCregs, which formally distinguishes them from other leukocytes, suggesting that they are the natural counterpart of BM-DCregs. Treatment of the recipient mice after alloHSCT with the recipient-type CD49+CD200R3+ cells as well as BM-DCregs protected against cGVHD, and the protection was associated with the generation of Ag-specific anergic CD4+ T cells as well as CD4+CD25+Foxp3+ regulatory T cells (Tregs) from donor-derived alloreactive CD4+CD25−Foxp3− T cells. In addition, the depletion of CD49+CD200R3+ cells before alloHSCT enhanced the progression of cGVHD. In conclusion, CD49+CD200R3+ cells act as naturally occurring DCregs to regulate the pathogenesis of cGVHD in alloHSCT mediated through the control of the transplanted alloreactive CD4+ T cells.
Databáze: OpenAIRE
Externí odkaz: