HARNESSING THE IMMUNE RESPONSE: BASIC PRINCIPLES AND THERAPEUTIC APPLICATIONS.

: The immune system responds to invaders (pathogenic microbes and cancer cells) but is tightly controlled to prevent harmful reactions against self tissues, commensal microbes, and the fetus. Elucidation of the molecular basis of these control mechanisms has been one of the most impressive recent advances in Immunology. Two of these mechanisms are particularly important and are being targeted therapeutically - inhibitory receptors (so-called checkpoint molecules) and a population of CD4+ T cells called regulatory T cells. This article summarizes how defining these mechanisms has opened new avenues for therapeutic manipulation of immune responses, and how experimental models, including transgenic and knockout mice we and others have used, have contributed to developing the critical knowledge base.