Delayed type hypersensitivity: Current theories with a historic perspective

Although the delayed type hypersensitivity (DTH) reaction was discovered over 100 years ago, the exact nature of the reaction has been the subject of contentious debate over the years. The reaction was discovered in 1882 by Robert Koch, but it was not until the 1940s that Landsteiner and Chase proved that the reaction was mediated by the cellular and not the humoral arm of the immune system. The first DTH reaction described used only the tuberculin antigen (tuberculin reaction), but the definition was later expanded to include cell mediated reactions to other bacterial and viral antigens, responses to pure protein with adjuvant or haptens, and host responses to allograft. The DTH skin test is used to test if prior exposure to an antigen has occurred. When small quantities of antigen are injected dermally, a hallmark response is elicited which includes induration, swelling and monocytic infiltration into the site of the lesion within 24 to 72 hours. This reaction has been shown to be absolutely dependent on the presence of memory T cells. Both the CD4+ and CD8+ fractions of cells have been shown to modulate a response. Contemporary debate regarding the reaction is focused on the role of the Th1 and Th2 cells originally discovered by Mosmann. It has been postulated that the Th1 cell is the "inducer" of a DTH response since it secretes interferon gamma (IFN ), a potent stimulator of macrophages, while the Th2 cell is either not involved or acting as a downregulator of the cell mediated immune response. Despite the early experimental success of this theory, experiments have shown that Th2 cells may be involved in certain types of proinflammatory cell mediated immunity. This review focuses on the nature of the different forms of DTH that can be elicited and the different experimental evidence that has led to the current theories regarding DTH and its role in cell mediated immunity.