The regulatory effect of adherent cells on lymphokine activated killer cells.

We analyzed the effect of adherent cells on the induction of lymphokine-activated killer (LAK) cell activity by depleting adherent cells from peripheral blood lymphocytes (PBL) or by adding adherent cells to PBL before culture with interleukin-2. We found that adherent cells clearly down-regulate LAK cell induction. These inhibitory effects are dependent on the number of adherent cells added. Inhibitory effects of adherent cells are abolished by the addition of indomethacin to the LAK culture. Soluble factors derived from adherent cells, such as interferons and interleukin-1, have a slight enhancing effect on LAK induction. In contrast, adherent cells appear to inhibit LAK induction primarily by producing prostaglandin E2(PGE2). PGE2 in turn inhibits the induction of LAK effector cells by inhibiting the expression of the transferrin receptor on LAK cells. These effects are manifested most strikingly in the early phases of LAK induction.