I-309 T CELL ACTIVATION GENE-3 CHEMOKINE PROTECTS MURINE T-CELL LYMPHOMAS AGAINST DEXAMETHASONE-INDUCED APOPTOSIS/

We have previously reported that cytokines such as IL-9, IL-4, and IL- 6 protect murine thymic lymphoma cell lines against dexamethasone-indu ced apoptosis. A similar activity, which could not be ascribed to any of these factors, was found in a number of human T cell supernatants t hat enabled mouse BW5147 thymic lymphoma not only to escape apoptosis but also to maintain proliferation. The protein responsible for this a ctivity was purified to homogeneity from the culture medium of activat ed leukemic T cells and was found to be identical with the I-309 chemo kine. Half-maximal anti-apoptotic activity was obtained with similar t o 1 ng/ml, a concentration considerably lower than that required for t he monocyte chemotactic activity of this molecule, as measured ore THP -1 cells. The purified I-309 also improved the survival of two other m ouse thymic lymphoma cell lines. This activity was as potent as that o f IL-9, which was the strongest anti-apoptotic factor found to date fo r these cells, Similar results were obtained for BW5147 cells with rec ombinant I-309 and with T cell activation gene-3, the murine homologue of I-309, but not with other members of the chemokine Family, includi ng IL-8, neutrophil-activating peptide-2, granulocyte chemotactic prot ein-2, macrophage inflammatory protein-la, RANTES (regulated upon acti vation, normal T cell expressed and secreted), monocyte chemotactic pr otein-1 (MCP-1), and MCP-2. MCP-3, however, showed a minor, but signif icant effect in this model. Unlike that of IL-9, the activity of I-309 was completely inhibited in the presence of pertussis toxin, indicati ng the involvement of a G protein in this process.