Macrophages May Activate or Destroy T Cells with Which They Form Antigen- or Coreceptor-Mediated Cellular Conjugates

The formation of antigen- or mitogen-mediated cellular conjugates with T cells enables macrophages to trigger in T cells costimulatory signals and to facilitate T cell clonal expansion and differentiation. The present study describes T cell death as an alternative consequence of T cell interaction with macrophages. Macrophages initiate the deletion of T cells which they target for conjugate formation through CD4 coreceptors. After suboptimal engagement, the TCR mediates a deletion program. Optimal TCR stimulation induces a rescue program which overrides the deletion program induced by suboptimal antigen receptor ligation or by coreceptor engagement. Evidence is presented suggesting that receptor clustering favors the transmission of activation signals, whereas ligation of nonclustered receptors facilitates T cell deletion.