当前位置： SCI文献检索 > TRANSPLANTATION PROCEEDINGS期刊下所有文献 > Injection of donor-derived OX62+ splenic dendritic cells with anti-CD4 monoclonal antibody generates CD4+CD25+FOXP3+ regulatory T cells that prolong allograft skin survival indefinitely and abrogate production of donor-specific antibodies in a rat model.

Injection of donor-derived OX62+ splenic dendritic cells with anti-CD4 monoclonal antibody generates CD4+CD25+FOXP3+ regulatory T cells that prolong allograft skin survival indefinitely and abrogate production of donor-specific antibodies in a rat model.

Abstract：

OBJECTIVE:To examine in a rat model the ability of donor dendritic cells and anti-CD4 monoclonal antibody (mAb) to generate donor-specific CD4+CD25+ regulatory T cells (Tregs) and to evaluate the capacity of these Tregs to prolong skin allograft survival and abrogate the production of donor-specific antibodies after skin grafting. MATERIALS AND METHODS:OX62+ (nonplasmacytoid) splenic dendritic cells were isolated from Fischer rats using magnetic beads and injected (2 x 10(6)) into Lewis rat recipients with or without treatment with a nondepleting anti-CD4 (W3/25) mAb. After 4 weeks, splenic CD4+CD25+FOXP3+ T cells were harvested using magnetic beads from conditioned animals and injected (1 x 10(6)) into naïve Lewis recipients (day 1) before they received a skin graft from a Fischer (n = 4) or a third-party (Norway; n = 4) donor rat. Donor-specific antibodies were detected in recipient blood using flow cytometric cross-matches with donor lymphocytes from day 0 to day 30 after grafting. RESULTS:After injection of conditioned CD4+CD25+FOXP3+ T cells, Lewis recipients accepted skin grafts from Fischer donors indefinitely (>100 days) but rejected third-party skin grafts. Donor-specific antibodies were detected at low levels in only 1 recipient receiving conditioned Tregs before grafting. Naive Tregs did not prolong skin graft survival. CONCLUSION:These preliminary data suggest that splenic dendritic cells in combination with an anti-CD4 mAb induce donor-specific Tregs that indefinitely prolong allogeneic skin graft survival and inhibit donor-specific antibody production. Experiments are under way to determine whether this protocol can inhibit chronic lesions after heart transplantation in this model.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Alawieh M,Rifle G,Bouchot O,Malapert G,Mousson C,Martin L

doi

10.1016/j.transproceed.2009.08.038

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

3363-6

issue

8

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(09)01231-7

journal_volume

41

pub_type

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