Related Experiment Video
Updated: Jun 21, 2026
Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique
Published on: October 12, 2014
CCR5 blockade in combination with rapamycin prolongs cardiac allograft survival in mice
1Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430022, China.
Abstract:
Both chemokine receptor 5 (CCR5) blockade and rapamycin (rapa) are effective in modulating transplant immunity and led to prolonged allograft survival, yet a great many grafts were ultimately lost to acute rejection. In this study we examined the inhibition of CCR5 in combination with the treatment with rapa in cardiac transplantation. Fully major histocompatibility complex-mismatched murine cardiac allograft models were randomized to five groups. They were administered with anti-CCR5 antibody or control antibody and rapa or phosphate-buffered saline (PBS), respectively. An additional group was treated with anti-CCR5 antibody, rapa and anti-CD25 antibody. Allograft rejection was investigated by flow cytometric analyses and enzyme-linked immunospot assay. Allografts treated with anti-CCR5 antibody plus rapa showed significantly prolonged survival (83 +/- 3 days, P < 0.001) compared with control antibody plus PBS-treated allografts (6 +/- 1 days). Treatment with anti-CCR5 monoclonal antibody (mAb) plus rapa inhibited significantly the progression of chronic rejction. Further analysis of donor hearts in the anti-CCR5 antibody plus rapa-treated group demonstrated increased infiltration of CD4(+)CD25(+)forkhead box P3(+) regulatory T cells, and depletion of CD25(+) cells resulted in acute rejection of allografts in 18 +/- 1 day. CCR5 blockade in combination with rapa is effective in preventing acute and chronic rejection in a robust murine model. This effect is mediated by CD25(+) T cell recruitment and control of T lymphocyte proliferation.
Insights
Combining chemokine receptor 5 (CCR5) blockade with rapamycin significantly prolongs cardiac allograft survival in mice. This combination therapy prevents acute and chronic rejection by recruiting regulatory T cells and controlling T cell proliferation.
Area of Science:
- Immunology
- Transplantation Immunology
- Pharmacology
Background:
- Chemokine receptor 5 (CCR5) blockade and rapamycin (rapa) individually modulate transplant immunity and prolong allograft survival.
- However, many allografts are still lost to acute rejection despite these treatments.
Purpose of the Study:
- To investigate the efficacy of combining CCR5 inhibition with rapamycin in cardiac transplantation.
- To elucidate the mechanisms underlying the combined therapeutic effect.
Main Methods:
- Utilized fully MHC-mismatched murine cardiac allograft models.
- Administered anti-CCR5 antibody, rapamycin, or both, with an additional group receiving anti-CD25 antibody.
- Assessed allograft rejection via flow cytometry and ELISpot assays.
Main Results:
- Anti-CCR5 antibody plus rapamycin significantly prolonged allograft survival (83 days vs. 6 days).
- Combined therapy inhibited chronic rejection progression and increased regulatory T cell infiltration (CD4+CD25+FoxP3+).
- Depletion of CD25+ cells led to acute rejection (18 days).
Conclusions:
- CCR5 blockade combined with rapamycin is effective in preventing acute and chronic rejection in a murine cardiac transplantation model.
- The therapeutic effect is mediated by CD25+ T cell recruitment and suppression of T lymphocyte proliferation.
