In Vitro Inhibition of Allogeneic CTL Generation and Interferon Gamma Production by the Cells of a Chemically Induced Fibrosarcoma

Abstract

We have previously shown that a highly tumorigeneic 3-methylcholanthrene transformed clone (MCA-C3H CL 15) of C3H10T1/2 fibroblasts and a normal nontransformed clone (C3H101/2 CL 8) from the same parental stock fail to stimulate the generation of syngeneic cytolytic effector cells. In attempting to further dissect and understand the immune response to these cells, we have extended our studies to examine their ability to stimulate the in vitro generation of allogeneic cytolytic effector cells. This model is unique in that studies of immune responses to tumor cells rarely have or utilize appropriate normal cell counterparts. The normal fibroblasts stimulated both the generation of allogeneic cytolytic T lymphocytes (CTL) and the production of immune interferon (IFN-γ), whereas the tumor fibroblasts did not. The normal fibroblasts were negative for mycoplasma, indicating that these organisms did not account for the observed IFN-γ induction. When added as third-party cells to cultures containing allogeneic responders and normal fibroblast stimulators, the tumor fibroblasts inhibited the generation of CTL as well as the production of IFN-γ. The absence of IFN-γ was not the result of the tumor fibroblasts absorbing or inactivating IFN-γ, since culturing the tumor cells in IFN-γ of predetermined activity did not appreciably alter that activity.