PHYSICAL INTERACTION WITH MONOCYTES RESCUES HUMAN MATURE CD4(-CELL LINES FROM ANTI-CD3-INDUCED APOPTOSIS() T)

Crosslinking of the TcR-CD3 complex with immobilized anti-CD3 antibodi es without sufficient co-stimulation induced cell death in human matur e CD4(+) T-cell lines. In these T cells, DNA fragmentation and morphol ogical characteristics of apoptosis were seen. The anti-CD3-induced ap optosis was inhibited by co-culture with monocytes. The rescue signal provided by monocytes does not need to be present simultaneously with signals mediated by anti-CD3. When T cells were precultured with monoc ytes for 24 h before anti-CD3 stimulation and then the monocytes were removed from the culture, anti-CD3-induced T-cell apoptosis was also i nhibited. To determine whether the monocyte-derived rescue signals wer e transduced by soluble factors or by direct cell-to-cell interaction with monocytes, we precultured T cells with monocytes separated by a m icropore membrane which prevented T cell-monocyte physical interaction but not the diffusion of secreted molecules. In this system, rescue s ignals could not reach the T cells. To further assess the importance o f physical interaction, we precultured T cells with fixed monocytes. T cells could not be rescued from apoptosis under these experimental co nditions, either. The results considered collectively suggest that suf ficient physical interaction with viable monocytes is important for th e rescue of anti-CD3-induced apoptosis of CD4(+) T cells.