酸素濃度のlymphokine activated killer(LAK), natural killer(NK)活性におよぼす影響 ： 養子免疫療法との関連において

Abstract

The culture of lymphocytes is usually performed in an incubator at the atmospheric oxygen concentration (about 20%). But in vivo lymphocytes exist in an oxygen concentration of less than 20%. I investigated the effects of various oxygen concentrations on lymphokine activated killer (LAK) and natural killer (NK) activities. The oxygen tension of arterial blood and venous blood are about 90～100 mmHg and 40 mmHg. The cultures were performed at 20%, 5%, and 2% oxygen concentrations using an N₂-O₂-CO₂ incubator, because the dissolved oxygen partial pressure of the culture medium is about 90 mmHg at 5% oxygen concentration and about 40 mmHg at 2% oxygen concentration in the incubator. The LAK and NK activities of the lymphocytes that were cultured with recombinant interleukin 2 (rlL-2) at 2% or 5% oxygen concentration for three days significantly decreased in comparison with those at 20% oxygen concentration. However, there was no difference in cell viability, CD-16 positive/Leu-7 negative cell population, or IL-2 receptor β (IL-2Rβ) chain positive cell population between the lymphocytes of the 2% oxygen culture and those of the 20% oxygen culture. The lymphocytes which were once activated with rlL-2 at 20% oxygen concentration for three days killed Daudi and K 562 cells under the condition of 2% oxygen concentration to the same degree as under that of 20% oxygen concentration. In other words, activated LAK and NK cells were capable of killing the tumor cells at 2% oxygen concentration, but oxygen is important for induction and maintenance of LAK and NK activities. Our results indicate the possibility that high levels of cytotoxic activity can be induced and preserved in vivo by oxygen supplement with breathing in the patient who receives adoptive immunotherapy against malignant tumor.