MONOCYTE-DERIVED MACROPHAGES PRIME PERIPHERAL T-CELLS TO UNDERGO APOPTOSIS BY CELL-CELL CONTACT VIA ICAM-1 LFA-1-DEPENDENT MECHANISM/

We designed the present study to clarify the mechanism of superantigen -induced apoptosis of human mature T cells and to elucidate the pivota l roles of monocyte-derived macrophages in induction of T cell apoptos is. Exposure of unfractionated human peripheral blood mononuclear cell s to SEA, SEE or PHA elicited apoptosis in T cells after 5-day culture . In purified T cell preparations, SEE was unable to induce apoptosis, but was inductive when the purified T cells were cocultured with mono cyte-derived macrophages adhering to plastic culture dishes. Placing t he T cells in the insert wells which physically separated them from th e adhering macrophages resulted in a complete loss of SEE-induced apop tosis. The addition of blocking antibodies against LFA-1, ICAM-1 and C D2 to the cocultures significantly inhibited the SEE-induced T cell ap optosis. We concluded therefore that direct contact of macrophages wit h T cells is critical in SEE-induced T cell apoptosis, and that adhesi on molecules such as LFA-1/ICAM-1 and CD2 may be involved in the mecha nism of this effect.