HLA-G-treated tolerogenic dendritic cells induce tolerogenic potential by increasing expression of B7-1 (CD80) molecules.
BACKGROUND
By consensus, HLA-G has a role in the induction of tolerance via interaction with dendritic cells and manipulation of co-stimulatory molecule expression. The purpose of this study was to demonstrate that HLA-G modified dendritic cells exhibit a decreased ability to stimulate T-cells in vitro due to increased expression of B7-1, which provides regulatory signalling to T-cells as a consequence of binding CD28 and CD152 ligands.


METHODS
Bone-marrow cells were cultured from Brown Norway (BN) rat femurs and sorted with anti-rat dendritic cell Ab (OX62) microbeads. Isolated dendritic cells (DCs) were treated with HLA-G tetramer for 3 days. Initially, cells were plated with media, alloantigenic splenocytes, and T-cells and then observed in mixed lymphocyte reaction for thymidine uptake. Also, the cells were analyzed by flow cytometry using antibodies for MHC-II (IA), CD80, and CD86.


RESULTS
This study displays that HLA-G-modified DCs decrease induction of an alloproliferative response. In addition, this study demonstrated that HLA-G tetramer treatment decreases CD86 and permits expression of CD80 without altering MHC-II expression.


CONCLUSIONS
This study specifically investigated the role of B7-1 (CD80), showing that HLA-G treatment of immature DCs allows expression of B7-1 (CD80) without altering MHC-II expression and simultaneously decreases B7-2 (CD86) expression. Therefore, a low level of B7-2 (CD86) allows attenuation of T-cell response after activation, both of which are beneficial to immune tolerance. The selective expression of B7-1 (CD80) is important and may serve as a guide for future therapies aimed at transplant tolerance.
Smith
M
M
Department of Surgery, Georgia School of Medicine, Augusta, Georgia, USA.
Bittner
J G
JG
White
S
S
Smith
D
D
Horuzsko
A
A
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005269:Femur; D018698:Glutamic Acid / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006680:HLA Antigens / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance; D051381:Rats; D011914:Rats, Inbred BN; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013977:Tibia; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology
D018122:B7-1 Antigen; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D018698:Glutamic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor