What is the role of T-lymphocyte surveillance in neoplastic disease?

Abstract

Dramatic advances have recently been made in our comprehension of how thymus-derived (T) lymphocytes function. Principles of both antigen-specific and nonspecific modes of their action in cell-mediated immunity are summarized as follows. First, different functions are carried out by distinct, separable populations of T lymphocytes. Second, all T-cell responses depend on interaction between cells of different functional subclasses. Thus, target cell killing of cytotoxic T lymphocytes depends on separate, coincident recognition of antigen by pre-cytotoxic T lymphocytes and by amplifier T cells that supply a nonspecific but critical lymphokine. Immunosuppressive drugs such as cyclosporin A and dexamethasone block this interaction at different points. Antigen-specific amplifier T cells also secrete various polypeptide factors that augment the impact of macrophage cytotoxicity, and immune interferon, which stimulates natural killer (NK) cells. Thus, even in cases where T cells are not the effectors, activation of T cells can potentiate host defenses. However, immune paralysis can result from stimulation of antigen-specific suppressor T cells. These act on effector cells directly or on their amplifier cells. The route of immunization often influences the balance between suppression and activation. Suppressor and amplifier T cells may be killed differentially by drugs like cyclophosphamide. Other cases of nonresponsiveness result from the way T cells actually recognize antigen. T cells only react with antigen in cell-surface complexes with self-histocompatibility antigen. Some otherwise-stimulatory antigens cannot form immunogenic complexes with the products of certain histocompatibility alleles, so that nonresponsiveness to those antigens is genetically predetermined. Overall, the centrality of T-lymphocyte surveillance in controlling spontaneous neoplasms is challenged by the low incidence of malignancy in T cell-deficient animals. This controversy will be examined both with reference to the lesions in T-cell development in these cases and with reference to the auxiliary roles played by T cells in amplifying the responses of non-T effector cells.