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Requirement of B7-H1 in mesenchymal stem cells for immune tolerance to cardiac allografts in combination therapy with rapamycin.

Abstract：

BACKGROUND:The potential of mesenchymal stem cells (MSCs) for immunosuppression has been tested in transplantation, but its mechanisms are not fully understood. This study investigated the role of MSC-expressing B7-H1 in the induction of immune tolerance to cardiac allografts by the combination therapy of MSCs and rapamycin (RAPA). METHODS:The anti-alloimmunity of donor MSCs in the presence or absence of RAPA was examined in both mouse cardiac allograft model (C57BL/6 to BALB/c mice) and a variety of cultured immune cells. Immunohistochemical staining was used for the measurement of intragraft antibody deposition, and fluorescence-activated cell sorting (FACS) for the determination of serum alloantibodies and leukocyte phenotypes. RESULTS:B7-H1 expression in cultured MSCs was up-regulated following IFN-γ stimulation. In transplant recipients, combination therapy of MSCs and RAPA induced immune tolerance to allografts, but blockade of B7-H1 on MSCs with monoclonal antibody abrogated the combination therapy-induced immune tolerance as heart allografts were rejected. The negative effect of MSC-expressing B7-H1 neutralization on graft survival was correlated with a reduction of regulatory immune cells (CD4(+)CD25(+)Foxp3(+) T cells, tolerogenic dendritic cells and IL-4(high)IL-10(High)CD83(low) B cells), and also with an increase in alloantibody (IgG and IgM) levels both inside the grafts and in the circulation as compared with un-neutralized controls. In vitro MSC-mediated suppression of antibody production and B cell proliferation depended on B7-H1 function and cell contact between CD19(+) B cells and MSCs. CONCLUSION:These data suggest that MSC-expressing B7-H1 mediates the immune tolerance to cardiac allografts in recipients receiving MSC and RAPA combination therapy.

journal_name

Transpl Immunol

journal_title

Transplant immunology

authors

Wang H,Qi F,Dai X,Tian W,Liu T,Han H,Zhang B,Li H,Zhang Z,Du C

doi

10.1016/j.trim.2014.06.005

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

65-74

issue

2

eissn

0966-3274

issn

1878-5492

pii

S0966-3274(14)00048-3

journal_volume

31

pub_type

杂志文章

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