Experimental models of cardiac transplantation: design determines relevance

Experimental models have contributed enormously to basic immunology. However, the use of reductionist experiments has produced results that are not always successfully translated into the clinic. Recently, incorporation of more realistic clinical parameters in experimental designs has produced new insights relevant to cardiac transplantation.

Experiments in mice have provided crucial insights into the concept that T cell responses to pathogens generate memory cells with cross-reactive specificities for histocompatibility antigens. These memory T cells are resistant to current immunosuppressive strategies. Memory T cells infiltrate grafts within hours after transplantation, and grafts subjected to clinically relevant periods of cold ischemia are more susceptible to injury by this cellular infiltrate. Early immune responses now can be investigated with improved 'humanized' mice. Mice with multiple knock-in genes for human cytokines support development of human monocytes, macrophages and natural killer cells in increased numbers and with better function.

Better and more clinically relevant experimental designs are providing animal models tailored to address clinic exigencies.