This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yang, S. C. Articles by Grimm, E. A. Search for Related Content PubMed Articles by Yang, S. C. Articles by Grimm, E. A.

Characterization of OKT3-initiated Lymphokine-activated Effectors Expanded with Interleukin 2 and Tumor Necrosis Factor ¹

Departments of Tumor Biology [L. O. S., E. A. G., J. A. R.], Thoracic Surgery [S. C. Y., J. A. R.], and General Surgery [E. A. G.], The University of Texas M. D. Anderson Cancer Center and the Department of General Surgery, University of Texas Health Science Center at Houston [S. C. Y.], Houston, Texas 77030

Synergistic and cooperative effects in vitro of OKT3, interleukin 2 (IL-2), and tumor necrosis factor (TNF) as stimuli in generating effectors with lymphokine-activated killer activity were studied. Activation of human peripheral blood mononuclear cells with OKT3 (10 ng/ml) for 48 h, followed by culture in low concentrations of IL-2 (10 units/ml) and TNF (250 units/ml) resulted in higher cell recovery (50- to 3300-fold) compared to the number of cells in the initial culture and enhanced lytic activity against both Raji and fresh lung tumor targets (mean 100-fold) by day 30 compared to those expanded with higher concentrations of IL-2 (100 units/ml) alone. Immunofluorescence analysis of peripheral blood mononuclear cells initiated with OKT3 and expanded with IL-2 plus TNF revealed a selective increase in CD8⁺ cells and a decrease in CD4⁺ by day 28; the opposite effect was observed when cells were incubated with 100 units/ml of IL-2 alone, resulting in a greater proportion of CD4⁺ cells. Almost all cells were CD3⁺. Studies of cytokine receptor expression indicated that OKT3 plus IL-2 plus TNF caused an earlier up-regulation of the IL-2 receptor ß chain (Tac) and higher TNF receptor expression by day 6 compared to 100 units/ml IL-2 alone. Significant TNF levels (>17 units/ml) were measured in culture supernatants from peripheral blood mononuclear cells initiated with OKT3 alone. Collectively, our data demonstrate that induction of lymphokine-activated killer activity with OKT3, followed by culture in low concentrations of IL-2 plus TNF is an alternative to the use of high-dose IL-2 alone and suggest that this combination may provide potential advantages in long-term generation of cytolytic cells.

¹ This project was supported by National Cancer Institute Grant RO1CA-45225 to E. A. G., by National Cancer Institute Thoracic Training Grant CA09611-01 to J. A. R., and by an award from the Preuss Foundation to E. A. G.

² To whom requests for reprints should be addressed, at the Department of Thoracic Surgery, Box 109, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 6/29/89. Revised 2/13/90.