Restoration of cytotoxic T lymphocyte function in malignant pleural effusion: Interleukin-15 vs. interleukin-2

The present study attempts to define the role of interleukin-15 (IL-15), as compared with IL-2, in generating cytotoxic T lymphocytes (CTL) from the m alignant effusions of cancer patients. Effusion-associated lymphocytes (EAL ) from malignant effusion were incubated with IL-15 or IL-2 with or without alpha CD3. Proliferation and cytotoxicity assays mere performed. IL-15 was found to have at least an equivalent, if not higher, activity to IL-2 in t erms of lymphocyte proliferation and generation of CTL from EAL, The prolif erative response of EAL, cocultured with IL-15, with or without alpha CD3, was partly inhibited by pretreatment with an anti-IL-2 receptor beta chain monoclonal antibody (mAb), The proliferative response of EAL, cocultured wi th alpha CD3, IL-2, or both, was partly inhibited by pretreatment with an a nti-IL-2 receptor alpha chain mAb, Overnight [Cr-51] release assays against K562, Daudi, and the patients' autologous tumor cells were done to evaluat e EAL's cytolytic activity. MHC class I Ab blocked the stimulated cytolytic activity of EAL against autologous tumors. An mAb depletion assay showed t hat the phenotype of the restored EAL was CD16(-)CD4(-)CD8(+); thus, the re stored activity of EAL was CTL activity. The results suggest that both IL-1 5 and IL-2 can restore CTL activity from EAL in the presence of T cell rece ptor (TCR)-CD3 engagement, but the effect of IL-15 was superior.