Immunity in the absence of autoimmunity reflects “self–nonself” discrimination by the immune system. The search for mechanisms preventing autoimmunity or enabling “self” tolerance has been at the root of immunology as evidenced by ample conceptual framework, rhetoric, sophism, and experimental data. A full understanding of such mechanisms would facilitate a large number of therapeutic interventions with immunity that are too diverse to be discussed here.
Of special interest is a pathway to self tolerance that involves regulatory or suppressor cells (also known as TReg cells). Curiously, these cells exhibit an anergic phenotype, being unable to proliferate upon TCR ligation in culture, at the very same time that their suppressive activity is manifested. This article recalls some of the early experiments that hinted at the existence of these suppressor cells—now a topic of intense investigation in several laboratories—and considers their dynamic nature in vivo, which...
