Purpose of review: Advances in the development of immunosuppressive drug regimens have led to impressive survival rates in the year following organ transplantation. However rates of long-term graft dysfunction remain undesirably high. Recently it has been shown that co-morbidities in the patient population may affect graft survival. In mouse models, hyperlipidemia, a co-morbidity present in the majority of cardiac transplant patients, can significantly alter T cell responses to cardiac and skin allografts, and accelerate graft rejection. Here we review recent advances in our understanding of how alterations in lipids affect immune function and graft survival.
Recent findings: Recent work in humans has highlighted the importance of controlling low density lipoprotein (LDL) levels in transplant recipients to reduce the development of chronic allograft vasculopathy (CAV). High serum levels of cholesterol containing particles leads to extensive immune system changes to T cell proliferation, differentiation and suppression. Changes in B cell subsets, and the ability of antigen presenting cells to stimulate T cells in hyperlipidemic animals may also contribute to increased organ allograft rejection.
Summary: Cholesterol metabolism is a critical cellular pathway for proper control of immune cell homeostasis and activation. Increasing evidence in both human, and in mouse models shows that elevated levels of serum cholesterol can have profound impact on the immune system. Hyperlipidemia has been shown to increase T cell activation, alter the development of T helper subsets, increase the inflammatory capacity of antigen presenting cells (APC) and significantly accelerate graft rejection in several models.
Keywords: T cells; Transplantation; co-morbidity; regulatory T cells.