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Cytokine Gene Expression during the Generation of Human Lymphokine-activated Killer Cells: Early Induction of Interleukin 1ß by Interleukin 2¹

Department of Anatomy, Loyola University, Maywood, Illinois [E. J. K.]; Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, Frederick, Maryland [S. K. B.]; and Laboratory of Molecular Immunoregulation, Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research Facility, Frederick, Maryland [D. L. L., L. V., H. A. Y.]

Culture of human peripheral blood leukocytes with interleukin 2 (IL-2) stimulates their differentiation into lymphokine-activated killer (LAK) cells, with a broad range of cytotoxicity against fresh tumor cells and tumor cell lines (Grimm et al., J. Exp. Med., 155: 1823–1841, 1982). We chose to utilize a molecular approach to determine whether IL-2 stimulates the expression of cytokine genes by the mixed cell population which may be involved in the generation or regulation of lytic activity. Northern blot analysis performed with total cellular RNA from LAK cells cultured for varying periods of time with IL-2 revealed that the genes which code for cytokines [interleukin 1 (IL-1) and ß, -interferon, tumor necrosis factor , and lymphotoxin] were not spontaneously expressed. As soon as 2 h after IL-2 treatment, IL-1 and IL-1ß mRNAs were expressed. Both nonadherent and adherent populations of LAK cells express IL-1ß mRNA; however, the adherent population produced more IL-1ß mRNA and maintained its expression for a prolonged period of time. Other cytokine mRNAs (-interferon, tumor necrosis factor , and lymphotoxin) were expressed later than the IL-1 mRNAs with maximal levels between Days 2 through 7. Our results indicate that LAK cell populations can generate a variety of cytokines which may be involved in the generation of lytic activity.

¹ Research sponsored, at least in part, by the National Cancer Institute, Department of Health and Human Services, under Contract NO1-Co-23910 with Program Resources, Inc.

² To whom requests for reprints should be addressed, at Department of Anatomy, Loyola University Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153.

Received 7/12/88. Revised 9/ 6/88. Accepted 11/18/88.