MACROPHAGES MAY ACTIVATE OR DESTROY T-CELLS WITH WHICH THEY FORM ANTIGEN-MEDIATED 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 signa ls 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 core ceptors. After suboptimal engagement, the TCR mediates a deletion prog ram. Optimal TCR stimulation induces a rescue program which overrides the deletion program induced by suboptimal antigen receptor ligation o r by coreceptor engagement. Evidence is presented suggesting that rece ptor clustering favors the transmission of activation signals, whereas Ligation of nonclustered receptors facilitates T cell deletion. (C) 1 998 Academic Press.