Immunosuppressive Effects of Mesenchymal Stem Cells: Involvement of HLA-G

Autor: Alain Chapel, Asma Boutarfa, Noëlle Mathieu, Sabine François, Christelle Mazurier, Sandrine Bouchet, N-Claude Gorin, Johanna Frick, Dominique Thierry, Aisha Nasef, Loic Fouillard
Přispěvatelé: CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Saas, Philippe
Rok vydání: 2007
Předmět:
T-Lymphocytes
Fluorescent Antibody Technique
Gene Expression
Graft vs Host Disease
MESH: Flow Cytometry
Lymphocyte proliferation
MESH: Histocompatibility Antigens Class I
0302 clinical medicine
HLA Antigens
MESH: Reverse Transcriptase Polymerase Chain Reaction
HLA-G
MESH: Fluorescent Antibody Technique
MESH: HLA Antigens
Cells
Cultured

0303 health sciences
biology
Reverse Transcriptase Polymerase Chain Reaction
MESH: Bone Marrow Cells
MESH: Immunosuppression
MESH: Enzyme-Linked Immunosorbent Assay
Flow Cytometry
3. Good health
030220 oncology & carcinogenesis
[SDV.IMM]Life Sciences [q-bio]/Immunology
Stem cell
MESH: Cells
Cultured

MESH: Gene Expression
[SDV.IMM] Life Sciences [q-bio]/Immunology
MESH: Graft vs Host Disease
Bone Marrow Cells
Enzyme-Linked Immunosorbent Assay
Human leukocyte antigen
Mesenchymal Stem Cell Transplantation
Major histocompatibility complex
03 medical and health sciences
Antigen
MESH: Cell Proliferation
Humans
MESH: Mesenchymal Stem Cell Transplantation
RNA
Messenger

Cell Proliferation
MESH: RNA
Messenger

030304 developmental biology
HLA-G Antigens
Immunosuppression Therapy
Transplantation
MESH: Humans
Histocompatibility Antigens Class I
Mesenchymal stem cell
Mesenchymal Stem Cells
Histocompatibility
MESH: Mesenchymal Stem Cells
MESH: T-Lymphocytes
Immunology
biology.protein
Zdroj: Transplantation
Transplantation, Lippincott, Williams & Wilkins, 2007, 84 (2), pp.231-7. ⟨10.1097/01.tp.0000267918.07906.08⟩
ISSN: 0041-1337
1534-6080
Popis: International audience; INTRODUCTION: Mesenchymal stem cells (MSCs) possess unique immunomodulatory properties. They are able to suppress allogenic T-cell response and modify maturation of antigen-presenting cells. Their role in the treatment of severe graft versus host disease has been reported. The underlying molecular mechanisms of immunosuppression are currently being investigated. Histocompatibility locus antigen (HLA)-G is a nonclassical major histocompatibility complex class I antigen with strong immune-inhibitory properties. METHODS: We studied the role of HLA-G on MSC-induced immunosuppression. The expression of HLA-G on human MSCs cultured alone and in mixed lymphocytes reaction (MSC/MLR) was analyzed. RESULTS: We found that HLA-G can be detected on MSCs by real-time reverse-phase polymerase chain reaction, immunofluorescence, flow cytometry (52.4+/-3.6%), and enzyme-linked immunosorbent assay in the supernatant (38.7+/-5.2 ng/mL). HLA-G protein expression is constitutive and the level is not modified upon stimulation by allogenic lymphocytes in MSC/MLR. The functional role of HLA-G protein expressed by MSCs was analyzed using the 87G anti-HLA-G blocking antibody in a MSC/MLR. We found that blocking HLA-G molecule significantly raised lymphocyte proliferation in MSC/MLR (35.5%, P=0.01). CONCLUSION: Our findings provide evidences supporting involvement of HLA-G in the immunosuppressive properties of MSCs. These results emphasize the potential application of MSCs as a relevant therapeutic candidate in transplantation.
Databáze: OpenAIRE