期刊
KIDNEY INTERNATIONAL
卷 78, 期 -, 页码 S18-S21出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2010.417
关键词
complement; heart transplant; innate immunity; natural killer cells; Toll-like receptors
资金
- National Heart, Lung, and Blood Institute [PO1HL018646, RO1HL093131]
- National Institute of Allergy and Infectious Disease of the National Institutes of Health [U19AI066705]
- Roche Organ Transplantation Research Foundation (ROTRF)
- International Society of Heart & Lung Transplantation (ISHLT)
The development of immunosuppressive drugs to control adaptive immune responses has led to the success of heart transplantation as a therapy for end-stage heart failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained clinical significance as mounting evidence now indicates that innate immune responses have important roles in the acute and chronic rejection of cardiac allografts including cardiac allograft vasculopathy (CAV). Whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and in the development of CAV. Stimulation of Toll-like receptors (TLRs), another important component of innate immunity, by endogenous ligands released in response to ischemia/reperfusion is now known to cause an inflammatory milieu favorable to graft rejection. Finally, new data indicate that activation of complement is linked to acute rejection and CAV. In summary, the conventional wisdom that the innate immune system is of little importance in whole-organ transplantation is no longer tenable. The addition of strategies that target TLRs, NK cells, and complement will be necessary to prevent CAV completely and to eventually achieve long-term tolerance to cardiac allografts.
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