Cross regulation by IL-10 and IL-2/IL-12 of the helper T cells and the cytolytic activity of lymphocytes from malignant effusions of lung cancer patients

Autor: Jacqueline Whang-Peng, Reury Perng Perng, Yuh Min Chen, Wen Kuang Yang, Den Mei Yang, Chou Chik Ting, Wen Ying Tsai
Rok vydání: 1997
Předmět:
Pulmonary and Respiratory Medicine
Cytotoxicity
Immunologic
Cellular immunity
Lung Neoplasms
Helper T lymphocyte
Lymphocyte
medicine.medical_treatment
Contrast Media
Centrifugation
Cell Separation
Adenocarcinoma
Critical Care and Intensive Care Medicine
Diatrizoate
Lymphocyte Activation
Immune tolerance
Lymphocytes
Tumor-Infiltrating
Th2 Cells
Aldesleukin
medicine
Immune Tolerance
Ficoll
Humans
Colloids
Lymphocytes
Killer Cells
Lymphokine-Activated
Cells
Cultured
business.industry
Povidone
T-Lymphocytes
Helper-Inducer
Th1 Cells
Silicon Dioxide
Interleukin-12
Recombinant Proteins
Interleukin-10
Pleural Effusion
Malignant
Killer Cells
Natural
Interleukin 10
medicine.anatomical_structure
Cytokine
Immunology
Interleukin 12
Interleukin-2
Cardiology and Cardiovascular Medicine
business
Immunocompetence
Zdroj: Chest. 112(4)
ISSN: 0012-3692
Popis: Study objective Our previous report demonstrated that there was impairment of local cellular immunity with elevated interleukin-10 (IL-10) and undetectable IL-12 in neoplastic pleural effusion. These findings suggest that the local immune reactions favor the T-helper type 2 (Th2) pathway instead of Th1 pathway. The present study was designed to examine whether local cellular immunity could be manipulated by IL-2 and/or IL-12 treatment, and to determine their effect on the helper T-cell pathways and the cytolytic activity of the effusion-associated lymphocytes (EALs). Design Using malignant pleural effusions obtained from four patients suffering from adenocarcinoma of lung, we separated the tumor cells from the EALs with Ficol-Hypaque centrifugation, followed by Percoll density centrifugation. To test whether the cytolytic function of lymphocytes could be enhanced by culturing with IL-2 and/or IL-12, lymphocytes were incubated with recombinant IL-2 with/without IL-12 for 6 days. Following this, the tumoricidal activity was assessed in an overnight 51 chromium-release assay. Autologous tumor cells for measuring specific antitumor activity, Daudi cells susceptible to lymphokine-activated killer cells, and NK-susceptible K562 cells were used as target cells. Measurements and results After treatment in vitro with IL-2, IL-12, or IL-2 plus IL-12, the Th pathway shifted from Th2 to Thl type (increased γ-interferon production). To further study the effect of cytokine treatment on the cytolytic activity of EALs, it was found that after 6-day culturing, the EALs failed to kill any of the three tumor targets, whereas the 6-day cultured peripheral blood lymphocytes (PBLs) gave low level of cytotoxicity against all three tumor targets. Stimulation with IL-2 alone partially restored the immunocompetence of EALs to kill the tumor targets. Stimulation with IL-12 alone showed no significant effect on their cytolytic activity. However, IL-12 synergized with IL-2 to increase the cytolytic activity of EALs and PBLs against autologous tumor targets. This synergistic effect was not found for Daudi cells and K562 cells. Conclusions These results suggest that EALs activated with IL-12 in the presence of a low concentration of IL-2, which converted the EALs from Th2 pathway to Thl pathway, could be an alternative source of antitumor effectors for adoptive immunotherapy of cancer.
Databáze: OpenAIRE
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