ABSTRACT
A non-interferon lymphokine elaborated from PHA and Con A-stimulated human T-cell hybridoma, T-CEMA, has been found to activate monocyte-derived macrophages for the intracellular killing of L. donovani (antileishmanial MAF). This T-cell hybridoma derived antileishmanial MAF which has an apparent mw of 65,000 and pI of 5.3-5.6, contains neither antiviral activity nor colony stimulating activity. Furthermore, antileishmanial MAF is not neutralized by anti-MIF, anti-IFN-gamma or anti-GM-CSF antibodies.
Subject(s)
Leishmania donovani/immunology , Lymphokines/physiology , Macrophage Activation , Animals , Antibodies, Monoclonal , Cell Line , Humans , Hybridomas/analysis , Isoelectric Point , Leishmania donovani/drug effects , Lymphokines/isolation & purification , Macrophage Activation/drug effects , Macrophage Migration-Inhibitory Factors/immunology , Macrophage Migration-Inhibitory Factors/isolation & purification , T-Lymphocytes/analysisABSTRACT
Recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) obtained from cloned complementary Mo cell DNA and expressed in COS-1 cells activates cultured peripheral blood monocyte-derived macrophages in vitro to become cytotoxic for intracellular L. donovani. The antileishmanial effect of rGM-CSF, which can be completely neutralized by anti-rGM-CSF antiserum, is maximal after 36 h preincubation with the cultured macrophages, compared with that of rIFN-gamma, which reaches its maximum at 72 h of preincubation. The antileishmanial effect of GM-CSF as well as IFN-gamma is independent of detectable amounts of LPS and is not augmented by the addition of 10 or 50 ng/ml of LPS. Simultaneous administration of suboptimal doses of rGM-CSF and rIFN-gamma to monocyte-derived macrophages results in greater antileishmanial activity by these cells than administration of either lymphokine alone, although no enhancement of antileishmanial activity is observed when optimal doses of these two lymphokines are applied together.
