Two mechanisms of migration inhibition factor induction by tumour antigens

Abstract

EVIDENCE has accumulated which stresses the importance of lymphokines in cell-mediated immunity both in vivo and in vitro¹. But, the processes leading to release of lymphokines by antigen-activated lymphocytes, the mode of action of these lymphokines and their exact role in cell-mediated immunity are still not well defined. It has, however, been recognised that in vitro activation of immune lymphocytes by soluble antigens is macrophage dependent and that this activation is under the control of gene products of the major histocompatibility complex (H–2 in the mouse)². Using a Moloney murine sarcoma virus (MSV)-induced tumour system, we have shown, in agreement with reports of some other systems^3,4, that immune T lymphocytes required macrophages for migration inhibition factor (MIF) production and, in addition, only histocompatible macrophages could assist immune T lymphocytes for MIF release after stimulation with soluble tumour-associated antigens⁵. We report here that gene products of the H–2 complex regulated the macrophage-immune lymphocyte interaction for MIF release when soluble tumour extracts were used as the source of antigen. In contrast, when intact tumour cells were used as the source of antigen, a macrophage requirement was not detectable. Moreover, the direct lymphocyte-tumour cell interaction for MIF release was not under H–2 restriction, since allogenic as well as syngeneic tumour cells could activate MIF release from immune lymphocytes. These findings suggest the existence of at least two different pathways for MIF production, reflecting perhaps the activation of two distinct sub-populations of T lymphocytes or the activation of T lymphocytes at two different stages of differentiation.