Alloantigen-Pulsed Host Dendritic Cells Induce T-Cell Regulation and Prolong Allograft Survival in a Rat Model of Hindlimb Allotransplantation

Yur Ren Kuo, Chong Wei Huang, Shigeru Goto, Chun Ting Wang, Li Wen Hsu, Yu Chun Lin, Kuender D. Yang, Chao Long Chen, W. P.Andrew Lee

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background: Composite tissue allotransplantation is restricted due to the risks presented by long-term therapeutic immunosuppression. This study is conducted to investigate whether treatment with recipient immature dendritic cells (DCs) pulsed with donor alloantigens can prolong allograft survival and induce T-cell regulation in a rodent model. Materials and methods: Orthotopic hindlimb transplants from Brown-Norway (RT1n) to Lewis (RT11) rats were performed (day 0). DCs were propagated from the recipient bone marrow and pulsed with the donor alloantigen lysate. Group 1 (control group) did not receive any treatment. Groups 2 and 3 received cyclosporine A (CsA) at a concentration of 10 and 16 mg · kg-1 · day-1, respectively, on days 0-20 following composite tissue allotransplantation. Group 4 received antilymphocyte serum (i.p. administered 4 d before and 1 d after transplantation) therapy. Group 5 received combined treatment with CsA (10 mg · kg-1 · day-1, days 0-20) and donor alloantigen-pulsed recipient DCs (i.v. administered on days 7, 14, and 21). Group 6 received combined treatment with CsA (10 mg · kg-1 · day-1 on days 0-20), antilymphocyte serum (administered i.p. 4 d before and 1 d after transplantation), and DCs (administered i.v. on days 7, 14, and 21). Graft rejection was defined as epidermolysis/desquamation of the donor skin. The mixed lymphocyte reaction was performed to determine the donor T-cell reactivity. Tissue samples were biopsied to analyze the histological changes, and flow cytometry was performed to quantify the donor T-cells. Results: Allograft survival was significantly prolonged (>200 d) in Group 6 when compared with the other groups (P < 0.001). The mixed lymphocyte reaction performed for Group 6 revealed hyporesponsiveness of the T-cells to donor alloantigens. Flow cytometric analysis in Group 6 revealed a significant increase in the percentage of CD4+/CD25+ and CD4+/foxP3+ T-cells expression, and significant increase in the percentage of donor cells (RT1n) in the recipient peripheral blood. Immunohistochemical staining of allo-skin revealed a significant increase in the proportion of CD25+ cells in the subcutaneous and dermis layers in Group 6, as compared to other groups. Conclusion: Treatment with donor alloantigen-pulsed recipient immature DCs in combination with transient immunosuppression prolongs allograft survival and induced tolerance by inducing T-cell hyporesponsiveness to donor alloantigens and increasing the CD4+/CD25+ T-cell population.

Original languageEnglish (US)
Pages (from-to)317-325
Number of pages9
JournalJournal of Surgical Research
Volume153
Issue number2
DOIs
StatePublished - May 15 2009
Externally publishedYes

Keywords

  • T-cell regulation
  • composite tissue allotransplantation
  • dendritic cell

ASJC Scopus subject areas

  • Surgery

Fingerprint Dive into the research topics of 'Alloantigen-Pulsed Host Dendritic Cells Induce T-Cell Regulation and Prolong Allograft Survival in a Rat Model of Hindlimb Allotransplantation'. Together they form a unique fingerprint.

  • Cite this