Double signal stimulation was required for full recovery of the autologous tumor-killing effect of effusion-associated lymphocytes

Chest. 2002 Oct;122(4):1421-7. doi: 10.1378/chest.122.4.1421.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Cell Division / drug effects
  • Cell Division / physiology
  • Cells, Cultured
  • Cytokines / pharmacology
  • Cytotoxicity, Immunologic / drug effects*
  • Cytotoxicity, Immunologic / physiology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / pharmacology
  • Interleukin-7 / pharmacology*
  • Lymphocyte Activation / drug effects
  • Pleural Effusion, Malignant / cytology
  • Receptors, Antigen, T-Cell / administration & dosage
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / physiology
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • Interleukin-12
  • Interferon-gamma