Phenotypic and functional analysis of human CD3 + and CD3− clones with “lymphokine‐activated killer” (LAK) activity. Frequent occurrence of CD3 + LAK clones which produce interleukin‐2

Clones capable of lysing fresh, uncultured tumor cells (“lym‐phokine‐activated killer”: “LAK” activity) were selected from microcultures derived from either E‐rosette‐positive or E‐ rosette‐negative cell populations. All the selected clones displayed a strong cytolytic activity against the NK‐sensitive K562 cell line. Two major phenotypic groups of clones could be identified: a first group expressed the CD3 differentiation antigen, present exclusively on mature T lymphocytes; however, in contrast to typical cytolytic T lymphocytes, the majority of these clones expressed the unusual CD4‐ CD8‐ phenotype, whereas the remainder were CD4‐ CD8 +. A second group was represented by CD3 ‐ clones which, in most instances, expressed the T‐cell‐lineage‐specific CD2 antigen. Following stimulation with phytohemagglutinin (PHA), most of the CD3 + LAK clones produced lnterleukin‐2 (1L‐2) and interferon‐γ (1FN‐γ) whereas those expressing the CD3 ‐ phenotype did not. Since previous studies indicated that PHA may be inefficient in inducing lymphokine production by T‐ cell variants lacking the CD3/T cell receptor complex (TCR), CD3 ‐ clones were further stimulated with the calcium iono‐phore A23187 plus phorbol 12‐myristate 13‐acetate (PMA). Only 2/11 CD3 ‐ LAK clones produced small amounts of IL‐2, whereas the majority released 1FN‐γ. Given the peculiar phenotypic and functional properties of many CD3 + LAK clones, we suggest that they may belong to a T‐cell subset distinct from typical CTLs.