Apoptosis of T lymphoma cells and its inhibition by monoclonal antibodies against cell surface adhesion molecules.

We previously established the malignant T lymphoma CS-21 cell line from a spontaneously developed lymphoma in a BALB/c mouse. CS-21 cells produce lymph node metastasis with a high incidence following s.c. injection. CS-21 lymphoma cells grew continuously when the cells were co-cultured under the cell-cell attached conditions with stromal cells prepared from lymph nodes. However, they were unable to proliferate by themselves and underwent apoptosis when separated from the lymph node stromal cells. To identify the cell adhesion molecules of CS-21, we developed monoclonal antibodies (mAbs) directed against CS-21 cell-surface proteins. Fourteen mAbs partially inhibited the binding of CS-21 cells to a CA-12 stromal cell monolayer. MCS-5 (mAb against CS-21 No. 5) directed against a 168-kDa cell-membrane protein and MCS-19 against a 23-kDa protein were found to suppress apoptosis and stimulate CS-21 cell growth. Soluble factors secreted from CA-12 stromal cells enhanced CS-21 cell growth but were not sufficient to prevent apoptosis. In the presence of both stromal cell-secreted factors and mAbs MCS-5 or MCS-19, CS-21 lymphoma cells resisted apoptosis and grew as quickly as in the co-culture with CA-12 stromal cells. Based on these results, we conclude that CA-12 lymph node stromal cells support CS-21 lymphoma cell growth by secreting paracrine growth factors and presenting receptors for the 168-kDa and 23-kDa cell surface adhesion molecules of CS-21 cells that transmit signals to prevent CS-21 cell apoptosis.