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(Chest. 2002;122:1421-1427.)
© 2002 American College of Chest Physicians

Double Signal Stimulation Was Required for Full Recovery of the Autologous Tumor-Killing Effect of Effusion-Associated Lymphocytes*

Yuh-Min Chen, MD, PhD, FCCP; Chun-Ming Tsai, MD; Jacqueline Whang-Peng, MD and Reury-Perng Perng, MD, PhD, FCCP

* From the Chest Department (Drs. Chen, Tsai, and Perng), Taipei Veterans General Hospital, and School of Medicine, National Yang-Ming University; and Division of Cancer Research (Dr. Whang-Peng), National Health Research Institute, Taipei 112, Taiwan, ROC.

Correspondence to: Yuh-Min Chen, MD, PhD, FCCP, Chest Department, Taipei Veterans General Hospital, 201, Sec. 2, Shih-Pai Rd, Taipei, Taiwan, ROC; e-mail: ymchen{at}vghtpe.gov.tw

Study objectives: To determine the different effects of interleukin (IL)-2, IL-4, IL-7, IL-10, IL-12, and/or T-cell receptor (TCR)-CD3 engagement in recovering the functions of cytotoxic T lymphocytes (CTL) from malignant effusion.

Setting: National teaching hospital.

Materials and methods: Effusion-associated lymphocytes (EAL) were isolated from 35 malignant pleural effusions. Interferon (IFN)-{gamma} production, proliferative response, and cytolytic activity of the cultured EAL against autologous tumors and K-562 cells were measured.

Results: It was found that EAL had a significantly depressed function. Stimulation with two signals, including IL-2 plus IL-7, IL-2 plus IL-12, or IL-2 plus TCR-CD3 engagement, could fully restore the functions of EAL, including IFN-{gamma} production, proliferative response, and a specific increase in cytolytic activity against autologous tumor cells. IL-4 and IL-10, whether or not in combination with IL-2, did not augment the function of EAL, and even depressed it in some cases. The lymphocyte-depletion test showed that most of the recovered functions were from CD8+ CTL.

Conclusion: The depressed cellular function of EAL could be reversed with double signal stimulation, including IL-2 plus IL-7, IL-2 plus IL-12, or IL-2 plus TCR-CD3 engagement. These recovered cellular functions were mainly from CD8+ CTL.

Key Words: interferon-{gamma} • interleukin-7 • interleukin-12 • lymphocyte function • malignant pleural effusion






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