Antigen-specific suppressor factor: missing pieces in the puzzle

Few areas of immunologic research have endured such strident criticism or engendered such fainthearted support as the study of antigen-specific suppression of the immune response. Although enjoying a modest resurgence as a means of promoting or maintaining peripheral tolerance to autoantigens, the study of antigen-specific suppression is not mainstream immunology. The field of immune regulation has, in fact, shifted focus toward explaining the data in terms of the Th1/Th2 paradigm. Indeed, the term suppression has been coopted, by those willing to use it, to describe the bioactivity of conventional cytokines, such as IL-4, IL-10 or TGF beta, which can be inhibitory in certain experimental models. In a very real sense, those who performed much of the early work in the field bear responsibility for the outcast status of suppression. With the increasing number of soluble mediators and cascades of interacting T cells, which populated reviews of the subject in the 1980s, the concept of antigen-specific suppression and suppressor factors simply became too complicated and was dismissed as artifact. Several laboratories have in the past few years made significant advances in the molecular characterization of antigen-specific TsF. Their work, as well as that of our own laboratory have established certain minimal molecular requirements for the expression of TsF bioactivity.