Immunosuppressive effects of mesenchymal stem cells : involvement of HLA-G

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.

Medienart:

Artikel

Erscheinungsjahr:

2007

Erschienen:

2007

Enthalten in:

Zur Gesamtaufnahme - volume:84

Enthalten in:

Transplantation - 84(2007), 2 vom: 27. Juli, Seite 231-7

Sprache:

Englisch

Beteiligte Personen:

Nasef, Aisha [VerfasserIn]
Mathieu, Noelle [VerfasserIn]
Chapel, Alain [VerfasserIn]
Frick, Johanna [VerfasserIn]
François, Sabine [VerfasserIn]
Mazurier, Christelle [VerfasserIn]
Boutarfa, Asma [VerfasserIn]
Bouchet, Sandrine [VerfasserIn]
Gorin, N-Claude [VerfasserIn]
Thierry, Dominique [VerfasserIn]
Fouillard, Loïc [VerfasserIn]

Themen:

HLA Antigens
HLA-G Antigens
Histocompatibility Antigens Class I
Journal Article
RNA, Messenger
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 28.08.2007

Date Revised 03.12.2021

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM17182430X