Although HER2/neu-targeted cancer vaccines have shown initial promise in the adjuvant setting, a therapeutic vaccine remains elusive due to the tumor escape mechanisms of established cancer. As described by Seavey et al. in this issue of CCR, a Listeria-delivered vaccine may help overcome immune tolerance, leading to an effective therapeutic vaccine.

How difficult is to go from egg to implanted embryo? The evolution of placentation in eutherian mammals created enormous challenges, in particular to the maternal immune system, as the fetus expresses paternal antigens that are capable of triggering immune rejection. Samstein et al. reveal a role for inducible regulatory T cells in the enforcement of maternal-fetal immune tolerance.

A specialized subset of epithelial cells in the thymus "promiscuously" transcribes thousands of peripheral genes to ensure that developing T cells can test their antigen receptors for dangerous autoreactivity. New findings by Takaba et al. indicate that the transcription factor Fezf2 acts independently of Aire in thymic epithelial cells to generate "genetic noise" for immunological tolerance.

Throughout their evolution, animals have developed mechanisms which protect them against parasites or infections by detecting and destroying foreign biological material within their own bodies. These mechanisms for excluding “non-self” biological materials whilst at the same time maintaining the integrity of the “self” have evolved for hundreds of millions of years into a highly complex body sy...

Long-term allograft survival is a major challenge facing solid organ transplantation. Recent studies have shown a negative correlation between infiltration of memory T cells and allograft survival. Furthermore, blockade of leukocyte activation increases acceptance of transplanted organs, including heart, liver, and kidney. Lung allografts are associated with high rates of rejection, and therapi...

Strategies for inducing immune tolerance are fundamentally similar across a spectrum of immune-mediated disorders, including allergic disease, autoimmunity, and rejection of allografts. In each case, the objective of establishing an immunoregulatory balance is challenged by variable upswings in effector cell populations and proinflammatory mediators of immunity, requiring careful, and innovativ...

Pregnancy is a temporary semi-allograft that survives for nine months. The importance of this event for the survival of the species justifies several tolerance mechanisms that are put into place at the beginning of pregnancy, some of which occur even at the time of implantation. The description of these mechanisms underlines the leadership of the trophoblast. The trophoblast is the conductor of...

Regulatory T cells (Tregs) play an indispensable role in maintaining immunological unresponsiveness to self-antigens and in suppressing excessive immune responses deleterious to the host. Tregs are produced in the thymus as a functionally mature subpopulation of T cells and can also be induced from naive T cells in the periphery. Recent research reveals the cellular and molecular basis of Treg ...