Cytotoxic effector cells of the immune system

Summary The organism contains several types of cytotoxic cells which are able to lyse host and foreign cells. Cytotoxic T-lymphocytes (CTL) appear to play the most important role among the killer cells but other lymphatic cells, such as natural killer (NK) cells and lymphokine-activated killer (LAK) cells as well as macrophages are also highly effective in the lysis of appropriate targets. The various cytotoxic effector cells differ distinctly concerning origin, phenotype, morphology and target cell specificity, but they bear the common feature that they destroy the target cells in a contact-dependent non-phagocytotic process.CTL are characterized by typical lysosomal granules and by the expression of a characteristic pattern of surface molecules. They recognize specific antigens which are presented in context with molecules of class I major histocompatibility complex (MHC). NK cells, on the other hand, kill the appropriate targets without prior immunisation and without requiring recognition of MHC molecules at the target cells. They also bear a typical pattern of surface markers which differ in several aspects from that of CTL. Human NK cells are further characterized by peculiar cytoplasmic granules with parallel tubular arrays which are not present in other cytotoxic cells. LAK cells constitute an additional, only recently described, killer cell population which arise from lymphatic cells in the presence of interleukin-2. They appear to represent a functional unique cytotoxic effector cell system with an exceptionally wide target cell spectrum including normal and malignant cells of different origin. LAK cells, however, show a profound heterogeneity concerning the expression of phenotype surface markers and it is not yet clear whether they are a unique cell line. By electron microscopy they display peculiar intranuclear inclusion bodies which may be associated with prolonged stimulation by interleukin-2. CTL, NK and LAK cells appear to possess similar mechanisms for cytolysis including secretion of pore-forming proteins, serine proteases and other proteins. Furthermore, they are able to trigger the cleavage of DNA in the target cell nucleus by a hitherto unknown pathway.Macrophages differ substantially from other cytotoxic effector cells concerning morphology, phenotype, kinetic of activation and target cell spectrum. They perform a variety of functions whereby contact-dependent target cell lysis represents only one of their properties. After target cell binding they release over 20 different molecules such as interleukin-1 and tumor necrosis-factor-alpha as mediators for cytolysis. Thus, macrophages appear like other cytotoxic effector cells to destroy their appropriate targets by different factors.Taken together the data obtained hitherto suggest that cellular cytotoxicity is mediated by various effector cells which may make a major contribution in the defence against infections and malignancies.Abbreviations ADCC antibody dependent cellular cytotoxicity - CD clone of differentiation - CTL cytotoxic T-lymphocyte - HTL helper T-lymphocyte - IL-2 interleukin-2 - LAK lymphokine-activated killer cell - LGL large granular lymphocytes - MHC major histocompatibility complex - NK natural killer cell - P1 perforin 1 - PTA parallel tubular arrays - TCR T-cell receptor complex