HLA-G-Treated Tolerogenic Dendritic Cells Induce Tolerogenic Potential by Increasing Expression of B7-1 (CD80) Molecules

M. Smith, J. G. Bittner IV, S. White, D. Smith, Anatolij Horuzsko

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Abstract

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. Discussion: 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.

Original languageEnglish (US)
Pages (from-to)1598-1603
Number of pages6
JournalTransplantation Proceedings
Volume40
Issue number5
DOIs
StatePublished - Jun 1 2008

Fingerprint

HLA-G Antigens
Dendritic Cells
T-Lymphocytes
Immune Tolerance
Mixed Lymphocyte Culture Test
Microspheres
Bone Marrow Cells
Femur
Thymidine
Flow Cytometry
Therapeutics
Ligands
Transplants
Antibodies

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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HLA-G-Treated Tolerogenic Dendritic Cells Induce Tolerogenic Potential by Increasing Expression of B7-1 (CD80) Molecules. / Smith, M.; Bittner IV, J. G.; White, S.; Smith, D.; Horuzsko, Anatolij.

In: Transplantation Proceedings, Vol. 40, No. 5, 01.06.2008, p. 1598-1603.

Research output: Contribution to journalArticle

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abstract = "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. Discussion: 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.",
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