Identification of a unique T cell-derived lymphokine that primes macrophages for tumor cytotoxicity

Macrophage activation factor (MAF) activity, assessed by the ability to activate macrophages (M∅) to lyse RBL - a TNF-resistant, retrovirally transformed, tumor target - was detected in the PHA-stimulated supernatant (Sup) of LBRM, a murine T cell line. LBRM Sup provided a priming signal to M∅, but required the subsequent addition of small amounts of LPS for the expression of tumor cytotoxicity. The identity of the lymphokine responsible for this MAF activity was investigated. IFN-γ, the only previously characterized lymphokine capable of priming M∅ for tumor cytotoxicity, did have MAF activity in the assay, but IFN-γ could not be detected by ELISA in LBRM Sup, and LBRM-derived mRNA lacked detectable message for IFN-γ. Moreover, anti-IFN-γ failed to inhibit the MAF activity of LBRM Sup, suggesting that the presence of small, undetectable amounts of IFN-γ were neither responsible nor required for LBRM MAF activity. LBRM MAF activity appeared distinct from the other previously identified lymphokines produced by LBRM, since granulocyte-macrophage-CSF, IL-2, and IL-3 purified from LBRM Sup were unable to activate M∅ to lyse RBL. IL-4 and TNF, two lymphokines not known to be produced by LBRM but able to activate M∅ for cytotoxicity of some tumor targets, were also unable to activate M∅ for RBL cytotoxicity. LBRM MAF lacked antiviral activity in biologic assays, further distinguishing the lymphokine from IFN-γ, and had an apparent M(r) of 30,000 Da using gel filtration chromatography. Thus, the LBRM T cell line produces a previously undescribed lymphokine that primes M∅ for tumor cytotoxicity.