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Chemokine receptor-dependent alloresponses
1Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318, USA. whancock@mail.med.upenn.edu
Immunological Reviews
|November 18, 2003
Summary
Targeting chemokine receptors can prolong allograft survival by controlling immune cell migration to transplants. This approach shows promise for improving transplant outcomes beyond traditional immunosuppression.
Area of Science:
- Transplantation immunology
- Molecular and cellular immunology
Background:
- Alloreactivity traditionally viewed as antigen presentation and effector cell expansion.
- Mechanisms of immune cell migration to allografts are increasingly important.
- Current immunosuppression has limited impact on leukocyte homing.
Purpose of the Study:
- To highlight the role of chemokine-dependent mechanisms in allograft rejection, acceptance, and tolerance.
- To provide a basis for understanding chemokine receptor-targeted therapies.
Main Methods:
- Dissection of chemokine-dependent leukocyte recruitment to transplants.
- Experimental targeting of chemokine receptors.
- Evaluation of immunosuppressive protocols' effects on chemokine production and leukocyte homing.
Main Results:
- Chemokine receptor targeting prolongs or induces permanent allograft survival.
- Alloresponses are preserved in secondary lymphoid tissues despite chemokine receptor targeting.
- Current immunosuppression has modest effects on chemokine production and leukocyte homing.
Conclusions:
- Chemokine-dependent mechanisms are critical for allograft fate.
- Targeting chemokine receptors offers a novel therapeutic strategy for allograft survival.
- Preclinical trials of chemokine receptor-targeted therapies are underway in primate models.