Functional differentiation of human lymphokine-activated killing (LAK) is distinct from expansion and involves dissimilar interleukin 2 receptors.
Human lymphocytes respond to IL-2 with the generation of MHC-unrestricted oncolytic activity. This function has been named lymphokine-activated killing (LAK). To investigate the mechanism by which IL-2 activates and maintains LAK, we have examined the role(s) of IL-2 cell surface receptors. Removal or blockade of unstimulated lymphocytes expressing the IL-2 receptor Tac does not preclude the acquisition of LAK function. Therefore, a non-Tac IL-2 receptor was proposed to be involved in LAK generation. Using direct 125I-IL-2 binding to Tac-negative LAK precursors suggested the existence of such an alternate IL-2 receptor. Chemical crosslinking of 125I-IL-2 to Tac-depleted lymphocytes followed by SDS-PAGE determined that the size of the non-Tac-binding protein was approximately 75 kDa. Tac-negative lymphocytes activated by a limited IL-2 pulse which was insufficient for detectable Tac upregulation indicated that an initial non-Tac pathway was involved in functional differentiation. The development of lytic function, Tac upregulation, and cellular proliferation was prohibited by trypsin, a treatment shown also to eliminate 125I-IL-2 binding to Tac-negative lymphocytes. The Tac antigen, although not involved in the initial generation of LAK, is involved in the proliferative maintenance of this lytic function.
D002454:Cell Differentiation; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2; D014357:Trypsin
D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D014357:Trypsin