The role of lymphotoxin in the IL-2-driven differentiation of human lymphokine-activated T-killer (T-LAK) cells in vitro.

Brief stimulation of human peripheral blood mononuclear cells with PHA and subsequent coculture with IL-2 results by 5 days in cultures of human lymphokine-activated killer (T-LAK) cells. While IL-2 drives the proliferation of these cells in vitro, their maturation into functional effector cells capable of cytokine secretion and cell cytokines depends on the presence of other cytokines. The role of LT in the differentiation and proliferation of human T-LAK cells in vitro was investigated. Higher levels of LT than TNF were secreted by T-LAK cells during the first 5 days of the primary culture, then secretion levels dropped sharply. Human T-LAK cells cultivated with anti-LT rabbit antisera showed a slight reduction in growth compared to normal rabbit serum controls. In contrast, phenotypic analysis by FACS showed a decrease in CD4+ and an increase in CD8+ populations of T-LAK cells in the treated cultures. Addition of LT from the beginning of the T-LAK cell culture resulted in an increase in CD4+ and a decrease in CD8+ cell populations at day 7. In addition, the cytolytic activity of non-MHC-restricted cytotoxicity and NK-like activity of anti-LT cultured T-LAK cells was also effected. These data indicated that LT may have a role in differentiation of IL-2 stimulated human T-LAK cells in vitro.