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Role of CXCR3 and CCR5 in allograft rejection

G T Schnickel1, G R Hsieh, C Garcia

  • 1Division of Cardiac Surgery, Department of Surgery, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California 90095, USA.

Transplantation Proceedings
|December 19, 2006
PubMed
Abstract

Insights

Blocking CXCR3 and CCR5 receptors significantly extended heart transplant survival in mice. This combined chemokine receptor blockade reduced immune cell infiltration, offering a promising strategy for controlling acute organ transplant rejection.

Area of Science:

  • Immunology
  • Transplantation Biology
  • Molecular Medicine

Background:

  • Chemokines mediate leukocyte trafficking and play a critical role in allograft rejection.
  • Specific chemokine-chemokine receptor interactions are vital in alloimmune responses, despite functional redundancy within the chemokine family.

Purpose of the Study:

  • To investigate the therapeutic potential of simultaneously blocking CXCR3 and CCR5 in acute allograft rejection.
  • To evaluate the impact of combined chemokine receptor blockade on immune cell infiltration and graft survival.

Main Methods:

  • A heterotopic heart transplantation model was established using CCR5-deficient mice undergoing transplantation from BALB/c to B6/129 recipients.
  • Experimental group mice received anti-CXCR3 serum, while controls received non-specific goat serum, without additional immunosuppression.
  • Allograft function was monitored daily via palpation, with graft survival confirmed by laparotomy.

Main Results:

  • Control group allografts were rejected rapidly, within 6 ± 1 days post-transplantation.
  • Combined blockade of CXCR3 and CCR5 significantly prolonged allograft survival, with all grafts surviving up to 24 days.
  • A notable decrease in CD4 and CD8 lymphocyte infiltration into the graft was observed in the experimental group at 24 days.

Conclusions:

  • Simultaneous blockade of CXCR3 and CCR5 effectively prolongs allograft survival in a fully MHC-mismatched murine model.
  • Combined chemokine receptor blockade demonstrates significant promise as a strategy to manage acute rejection in organ transplantation.

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