Control of apoptosis and growth of malignant T lymphoma cells by lymph node stromal cells.

We have previously established the malignant T lymphoma CS-21 cell line from a spontaneous lymphoma in a BALB/c mouse. CS-21 lymphoma cells grew continuously when they were cocultured with stromal CA-12 cells prepared from lymph nodes. CS-21 lymphoma cells, however, could not proliferate by themselves, and they underwent apoptosis when separated from the stromal CA-12 cells. Apoptosis of CS-21 lymphoma cells was determined by observation of morphological changes using a transmission electron microscope and also by detection of nuclear DNA degradative fragments of oligonucleosomal size. Stromal CA-12 cells secreted soluble factors that enhanced DNA synthesis in CS-21 lymphoma cells. The soluble factors, however, were not sufficient to prevent apoptosis of CS-21 cells. Apoptosis of CS-21 lymphoma cells was suppressed only when the CS-21 lymphoma cells were cocultured with substantial numbers of CA-12 cells. The results suggest that the lymph node stromal CA-12 cells played an important role in the growth of CS-21 lymphoma cells by providing at least two different signals. One signal prevented CS-21 cells from apoptotic cell death by direct cell-to-cell contact, and the other signal enhanced the CS-21 cell proliferation by secreted soluble factors.