Antigen-induced death of T-lymphocytes

Resting mature T-lymphocytes are activated when they are triggered via thei r antigen-specific T-cell receptor (TCR) molecule or the associated CD3 ant igen. In contrast, preactivated I-cells can undergo activation-induced cell death (AICD) in response to the same signals. Stimulation of activated T-c ells upregulates the expression of the Fas-ligand, and the interaction of F as-ligand with the corresponding Fas receptor triggers an apoptosis program that culminates in cellular suicide usually associated with the fragmentat ion of DNA into oligonucleosomal bands. Molecular evidence indicates that p roteases related to interleukin-1-beta converting enzyme play an essential role in the execution of cell death. AICD of mature T-lymphocytes can be ef ficiently triggered by monoclonal antibodies against the CD3/TCR complex, o r by superantigens such as bacterial enterotoxins. Although it is more diff icult to induce AICD by conventional peptide antigens, it is now clear that antigen-induced AICD is a powerful means of eliminating antigen-reactive T -cells. Therefore, AICD contributes to the regulation (i.e., termination) o f cellular immune responses. In addition, AICD might play a role in the est ablishment of peripheral immune tolerance. Increased knowledge of the molecular mechanisms of AICD opens new immunothe rapeutical perspectives for the treatment of certain autoimmune diseases, a nd will have implications in other areas such as transplantation medicine.