CELLULAR IMMUNOLOGY 118,458-469 ( 1989) Selective Lysis of Target Cells by Interleukin-2-Expanded Peripheral Blood Mononuclear Leukocyte Clones’ BENJAMIN P. CHEN,*JACQUELYN A.HANK,* ERICE.KRAUS,* AND PAUL M. S~NDEL*~~X~Y~ Departments of *Human Oncology, TPediatrics, and $Genetics, University of Wisconsin, Madison, Wisconsin 53792 Received August 23, 1988; accepted October IO, I988 The presence ofdistinct cytolytic subsets within interleukin-2-expanded peripheral blood leu- kocytes (IEL) cultures was demonstrated by clonal analysis. Thirty-seven IEL clones were iso- lated from two healthy blood donors; 2 1 destroyed both Daudi and K562 cell lines. Of those 2 1 clones, 1 clone could destroy autologous PBM, 7 clones could destroy fresh allogeneic ovarian carcinoma (OVA-CA) cells, and 6 clones could destroy normal autologous PBM and fresh OVA- CA cells. Twelve of the 37 clones destroyed only one of the four targets tested: 8 clones destroyed K562,2 clones destroyed Daudi, and 1 clone each was selective for autologous PBM or OVA- CA. Of the remaining 4 clones, 1 destroyed OVA-CA and Daudi cells, 1 destroyed PBM and K562, 1 destroyed PBM and Daudi cells, and 1 destroyed PBM, Daudi, and OVA-CA. These results suggest that these functionally heterogeneous cytolytic clones may use different cell recog- nition or cytolytic mechanisms to enable these distinct and, at times, reciprocal patterns of target cell selectivity. 0 I989 Academic Press, Inc. INTRODUCTION Activation of human peripheral blood mononuclear leukocytes (PBM) with IL-2 generates phenotypically heterogeneous populations of effector cells which mediate non-MHC-restricted cytotoxicity of various tumor cell lines, fresh tumor cells, and to a lesser extent, normal vascular endothelial cells and PBM ( 1- 13). This non-MHC- restricted cytotoxicity has been designated the lymphokine-activated killer (LAK) phenomenon (1, 2). The heterogeneity of cell phenotypes mediating the LAK phe- nomenon could suggest that IL-2 induces diverse populations of lymphoid cells to nonspecifically lyse both tumor and normal cells, or that IL-2 expands subsets of IEL with different target cell “selectivities.” Data are consistent with both of these two mutually nonexclusive possibilities (5- 12). Skinner et al. (5) and Brooks et al. (6, 7) have shown that Sendai virus-specific and alloantigen-specific cytotoxic T cell clones (CTL), upon exposure to a high concentration of IL-2, become nonspecific killer cells capable of destroying both natural killer (NK)-sensitive and NK-resistant target cells. While Philips and Lanier (8) Ortaldo et al. (9), and Ferrini et al. (10) have reported ’ This study was supported by Grants NIH-CA 32685 and American Cancer Society CH-237. ’ To whom correspondence should be addressed at K4/448 UWCCC, 600 Highland Ave., Madison, WI 53792. 458 0008-8749/89$3.00 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.