Cytotoxicity of Human Lymphocytes: Antagonism between Inducing Processes

Abstract

CELL-MEDIATED immunity is of fundamental importance for transplantation immunity and delayed hypersensitivity reactions. The actual mechanism by which the immunologically triggered lymphocytes exert their effect is unclear, but it is known that the reactions obey immunological rules of specificity. Initiation of the reactions is probably based on immunological recognition. By the development of in vitro techniques to investigate cell-mediated immunity, the specificity of cytotoxic reactions caused by lymphocytes from sensitized donors has been confirmed. These techniques also led to the discovery that non-sensitized lymphocytes could exert a cytotoxic effect on target cells in vitro^1–4, provided the lymphocytes were stimulated by certain substances or processes. During studies of various reactions responsible for triggering human lymphocytes into a cytotoxically active state, it was found that lymphocytes exposed to one inductive agent became unresponsive to another which by itself could initiate cytotoxicity. This suggests the existence of previously unknown pathways of lymphocyte reactivity, which may be important in understanding the mechanism of lymphocyte cytotoxicity in graft rejection, and of cellular pathways for the establishment of unresponsiveness in previously competent lymphocytes, which may be important in cellular reactions involved in immunological tolerance.