Defect in generation of LAK cell activity under oxygen-limited conditions

In general, the in vitro induction of lymphokine activated killer (LAK) cell activities by interleukin 2 (IL-2) in human peripheral blood mononuclear cells (PMNC) has been performed in an atmosphere of 5% CO2 in air (20% O2), whereas IL-2-induced LAK cell activities are considerably reduced under concentrations of 5% O2 equal to arterial blood oxygen tension (100 mmHg) and 2% O2 equal to venous blood oxygen tension (40 mmHg). Cultured cell viability, IL-2 receptor-beta expression on large granular lymphocytes (LGL), the percentage of IL-2 receptor-beta positive LGLs and cell proliferation were not affected by oxygen-limited conditions. LAK cells were induced by IL-2 over 5 days at 20% O2, at which time the LAK cells were further stimulated by IL-2 in 2% O2 and 20% O2. Under these conditions the activity of LAK cells in 2% O2 decreased day by day, while that of LAK cells induced in 20% O2 was maintained at least until day 10 of the original culture. LAK effector cell-mediated lysis was not influenced by oxygen-limited conditions. These results point to more successful applications of the combination of oxygen therapy and adoptive cellular immunotherapy in the clinic.