Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells

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Abstract
Culture of human peripheral blood lymphocytes (PBL) in partially purified and lectin-free interleukin 2 results in the generally of cytotoxic effectors cells which have the unique property of lysing natural killer (NK)-resistant, fresh, human tumor cells. These effector cells have been termed lymphokine-activated killer cells (LAK). LAK are generated from both normal and cancer patients'' PBL and are able to lyse both autologous and allogeneic tumor cells from all histologic tumor types tested. Previous studies suggested that the LAK phenomenon was distinct from either the cytotoxic thymus-derived lymphocyte (CTL) or NK systems based on a variety of criteria. This study reports that the cell type involved is also distinct, as determined by phenotypic characteristics. The LAK effector cell phenotype was analyzed in parallel with alloimmune CTL, and LAK were similarly susceptible to the monoclonal anti-T cell antibodies OKT-3 or OKT-8 plus complement. The LAK precursor was not susceptible to the OKT-3 or Leu-1 antibodies plus complement, while the ability to generate alloimmune CTL was totally obliterated when tested using the same PBL responder population; generation of LAK was augmented 5- to 6-fold, clearly suggesting that LAK precursor cells are not T lymphocytes as defined by these antibodies. LAK precursors were abundant in NK cell-enriched Percoll gradient fractions, which had been depleted of the 29.degree. C E[erythrocyte]-rosetting high affinity T cells. LAK precursors were distinct from the majority of NK cells, since lysis of fresh PBL with the monoclonal antibodies OKM-1, Leu-7 or OKT-11 significantly depleted or totally eliminated NK activity, while subsequent activation of the remaining cells generated high levels of LAK and, in some cases, augmented levels of LAK. LAK precursors were distributed in the thymus, bone marrow, spleen, lymph node and thoracic duct in addition to the PBL. Therefore, while the cell(s) responsible for activation and expression of LAK activity have some common features with the classic T cell-mediated CTL and NK cell systems, the LAK precursor cells are clearly distinct, as determined by phenotype analysis using monoclonal antibodies and complement, and, at present, must be classified as a null cell.