Mechanisms of T-cell activation

Rapid progress has been made in our understanding of positive and negative regulatory mechanisms of T-cell activation. A number of signals, either antigen-specific via the T-cell receptor, or nonspecific (i.e. cytokines, costimulation) are involved. The most important costimulatory signals for T-cell activation are probably cell-cell interactions through membrane bound ligand-receptor pairs in an organized contact interface between the T cell and the APC, termed the 'immunological synapse' (IS). Following a TCR-mediated signal, the costimulatory signal delivered by CD28 promotes T-cell activation, whereas CTLA-4 inhibits early events in T-cell activation, e.g., the transcription of the IL-2 gene and the upregulation of G1-kinases. Positive and negative signal transduction is also promoted by certain adapter molecules showing that T-cell activation is regulated by a dynamic interplay of positive and negative signals.