The influence of the cellular infiltrate on the evolution and intensity of delayed hypersensitivity reactions.

When a delayed-type hypersensitivity (DTH) reaction is elicted in a sensitive animal at a skin site in which an accumulation of mononuclear cells has been induced by a prior injection of a nonspecific stimulus, those properties characteristic of a DTH reaction, i.e. erythema, edema, and induration, become evident much more rapidly and intensely than a reaction in an unprepared skin site. This rapid, intense reaction has the histology of a classical delayed reaction and persists as long or longer than a classical DTH reaction in the same animal. Two facts are evident from these observations. Firstly, early in the development of a delayed reaction, the slow accumulation of mononuclear cells may be completely independent of the presence of specific antigen. Secondly, there is a reaction between specific antigen and an antibody-like substance which may or may not be attached to cells. The reaction develops so rapidly at a prepared site that the pharmacological mediators which are responsible for edema must be presumed to be released abruptly. A classical delayed reaction is attributable to the time needed for the accumulation of cells in sufficient numbers. It follows that the rate-limiting step in a classical delayed reaction is the process of cell accumulation. The present observations indicate that this process is independent of the presence of specific antigen.