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Related Experiment Video

Updated: Jul 13, 2026

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
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CCR5 blockade modulates inflammation and alloimmunity in primates.

Carsten Schröder1, Richard N Pierson, Bao-Ngoc H Nguyen

  • 1Division of Cardiac Surgery, Department of Surgery, University of Maryland and Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|August 7, 2007
PubMed
Summary

CCR5 antagonists show promise in reducing transplant rejection and inflammation. Combining CCR5 antagonist CMPD 167 with cyclosporine A improved cardiac allograft survival and suppressed vasculopathy in primates.

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Area of Science:

  • Immunology
  • Transplantation
  • Pharmacology

Background:

  • CCR5 receptor antagonism is effective for HIV but its role in inflammation and immunity is under investigation.
  • CCR5-bearing cell recruitment into allografts signifies acute rejection and may predict chronic rejection.
  • Renal transplant patients with nonfunctional CCR5 receptors rarely experience late graft loss.

Purpose of the Study:

  • To explore the effects of the CCR5 antagonist CMPD 167 in a primate cardiac allograft model.
  • To evaluate CMPD 167's impact on perioperative stress responses and leukocyte recruitment.
  • To assess the combination of CMPD 167 and cyclosporine A in modulating alloimmunity and graft survival.

Main Methods:

  • Utilized a cynomolgus monkey cardiac allograft model.
  • Administered the CCR5 antagonist CMPD 167.
  • Compared monotherapy with combination therapy (CMPD 167 and cyclosporine A).

Main Results:

  • Perioperative stress responses and CCR5-bearing leukocyte infiltration were reduced with CMPD 167 monotherapy.
  • Anti-CCR5 monotherapy provided only marginal prolongation of allograft survival.
  • Combination therapy delayed alloantibody production, suppressed cardiac allograft vasculopathy, and tended to prolong graft survival compared to cyclosporine A monotherapy.

Conclusions:

  • CCR5 antagonism is a potential therapeutic strategy for mitigating postsurgical stress responses.
  • Targeting CCR5 favorably modulates pathogenic alloimmunity in primates, including humans.
  • Combination therapy with CCR5 antagonists and standard immunosuppressants may enhance transplant outcomes.