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The ability to activate peripheral blood lymphocytes (PBLs) in vitro with interleukin‐2 (IL‐2) is suppressed by the presence of autologous human pulmonary alveolar macrophages (AMs). AMs suppress both IL‐2‐induced proliferation and the induction of lympho‐ kine‐activated killer cell (LAK) activity in a dose‐ dependent manner (79 ±6% suppression of LAK activity at a 0.25:1 AM/PBL ratio). Increasing the IL‐2 concentration increased baseline LAK activity but did not prevent AM‐mediated suppression. At least two different mechanisms of suppression were observed, one diffusible in nature and the other contact dependent. Indomethacin prevented the component of inhibition that diffused across porous polycarbonate membranes, indicating prostaglandins as the diffusible inhibitor. In contrast, indomethacin had no effect when added alone into conventional AM‐ PBL cocultures, but a combination of indomethacin and anti‐transforming growth factor β1(TGF‐β1)antibody did prevent inhibition. This result suggests that TGF‐ß1acts as an additional contact‐dependent inhibitor. PBLs that were rendered unresponsive to IL‐2 completely recovered their responsiveness within 4days after removing AMs from the coculture. These features suggest that pulmonary macrophages have multiple mechanisms for locally suppressing IL‐2 responses and lymphocyte activation.

• Tumor-infiltrating lymphocytes (TILs) show depressed natural killer (NK) activity compared with peripheral blood lymphocytes (PBLs). To determine if TIL NK function can be reactivated in vivo, 11 patients with tumors metastatic to the lung were treated with systemic recombinant interleukin 2 (rlL-2). Spontaneous TIL NK activity and NK activity after three days' incubation with 100 U/mL of rlL-2 were increased in patients receiving 15000 U/kg of rlL-2 preoperatively compared with those receiving between 1000 and 10000 U/kg. Histologically, higher doses of rlL-2 increased the number of intratumoral lymphocytes, the level of peritumoral lymphocytic transferrin, and the expression of HLA-DR. Spontaneous PBL NK activity in patients receiving between 10000 and 15000 U/kg of rlL-2 was also increased and was further increased by in vitro culture with rlL-2. Thus, PBL NK activity and TIL NK function in vivo can be augmented with 15000 U/kg of systemic rlL-2. Both TIL- and PBL-inducible cytotoxicities were further enhanced by in vitro culture with rlL-2.(Arch Surg 1987;122:1446-1450)