PROLIFERATION, PHENOTYPE, AND CYTOTOXICITY OF HUMAN-LYMPHOCYTES ISOLATED FROM LYMPH-NODES INVADED BY MELANOMA-CELLS

The effects of human recombinant interleukin-4 (rIL-4) on metastatic m elanoma (lymph node)-derived T lymphocytes cultured with human recombi nant interleukin-3 (rIL-2) were studied. Lymphocytes isolated from mel anoma-invaded lymph nodes were cultured in media with rIL-2 in the pre sence (MB-2,4) or absence (MB-2) of rIL-4 for up to 48 days. A majorit y of lymphocytes grown in both cultures were CD3(+) T lymphocytes. Add ition of rIL-4 to the rIL-2 culture abrogated the growth of the CD3(-) , CD56(+) cell population [natural killer (NK) cell], which were prese nt in culture with rIL-2 alone. Lymph-node-derived T lymphocytes that had expanded under MB-2,4 conditions lysed only autologous melanoma ce lls and they maintained the autologous-specific cytolytic activity dur ing the entire culture period. They did not lyse K562, Daudi, or allog eneic target cells. Monoclonal antibodies (MAbs) against CD3 molecules and MHC class I molecules but not MHC class II molecules inhibited th e specific lytic functions of T lymphocytes under MB-2,4 culture condi tions. Collectively, these data indicate that in lymphocyte culture de rived from melanoma-invaded lymph nodes, rIL-4 inhibits the rIL-2-depe ndent proliferation of NK cells and antigen nonspecific killer T lymph ocytes and also effectively abrogates the rIL-2-induced NK and lymphok ine-activated kilter (LAK) activities.