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


METHODS
National teaching hospital.


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.


CONCLUSIONS
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.
Chen
Yuh-Min
YM
Chest Department, Taipei Veterans General Hospital, 201, Sec. 2 Shih-Pai Road, Taipei, Taiwan, ROC. ymchen@vghtpe.gov.tw
Tsai
Chun-Ming
CM
Whang-Peng
Jacqueline
J
Perng
Reury-Perng
RP
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016066:Pleural Effusion, Malignant / Q000166:cytology; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12; D007371:Interferon-gamma