ABSTRACT
This chapter focuses on aspects of our current research on interleukin-2 (IL-2) and the immunoregulatory properties by two other well-characterized cytokines, tumor growth factor-β (TGF-β) and tumor necrosis factor, as they affect the IL-2-driven induction and maintenance of human lymphokine-activated killing (LAK) oncolysis. To date, perhaps no single cytokine has proved to be as contributory as IL-2 in facilitating our understanding of immunoregulation by soluble factors. Although the functional role of IL-2 was first realized in the proliferation of antigen-specific cytotoxic T lymphocytes, it was later shown to be of tantamount importance in the direct activation of “nonclassical” lymphocyte cytotoxicity, termed lymphokine-activated killing. In addition to the diminution of effector cytotoxic function, cellular proliferation was reduced approximately twofold when TGF-β was present. Our own investigations strongly suggest that the microenvironmental conditions employed for in vitro LAK generation can greatly influence both the phenotype and function of the effector cell generated.
