Tolerogenic dendritic cells: all present and correct?

Although well-recognized for their sentinel role and, when activated, their immunostimulatory function, bone marrow-derived dendritic cells (DC) possess inherent tolerogenic (tol) ability. Under quiescent conditions, these cells maintain central and peripheral self tolerance. When appropriately conditioned, in vitro or in vivo, they inhibit innate and adaptive immunity to foreign antigens, including memory T-cell responses. This suppressive function is mediated by various mechanisms, including the expansion and induction of antigen-specific regulatory T cells. Extensive experience in rodent models and recent work in nonhuman primates, indicate the potential of pharmacologically-modified, tol DC (tolDC) to regulate alloimmunity in vivo and to promote lasting, alloantigen-specific T-cell unresponsiveness and transplant survival. While there are many questions yet to be addressed concerning the functional biology of tolDC in humans, these cells offer considerable potential as natural, safe and antigen-specific regulators for long-term control of the outcome of organ and hematopoietic cell transplantation. This minireview surveys recent findings that enhance understanding of the functional biology and therapeutic application of tolDC, with special reference to transplantation.