Dieter Kabelitz & Ottmar Janssen

Department of Immunology, Paul-Ehrlich-Institute, Langen, Germany

Received 1/24/97; Accepted 1/31/97 On-line 2/15/97

It is obvious that the induction or prevention of AICD in peripheral T-lymphocytes is a complex process that is regulated by multiple signals, only some of which have been discussed here. Depending on the experimental system, AICD is modulated by cytokines (46, 83-85, 172-175) and costimulatory signals (141, 176). In this review, we have focussed on AICD of peripheral T-cells triggered through signaling via the CD3/TCR complex. There are other clinically important situations where a disturbance of apoptosis is suspected to contribute to the pathogenesis of the disease. Several reviews have recently discussed the possible role of apoptosis in the progressive loss of CD4⁺ T-cells during HIV infection (e.g., ref. 177). Therefore, this aspect has not been discussed here. Moreover, there is increasing evidence that apoptosis is an important parameter contributing to the regulation of the interaction between tumor cells and the immune system. It is obvious that a defective capacity to undergo physiological programmed cell death could form the basis for uncontrolled growth of tumor cells. Perhaps more importantly, tumors may also actively prevent T-cells from cell-mediated tumor cell attack through the exploration of the Fas/Fas-L system. This hypothesis is supported by the recent demonstration that some tumor cells constitutively express the Fas-L, thus inducing apoptosis in tumor-infiltrating Fas⁺ T-lymphocytes (178, 179). This may be an important mechanism of immune escape of tumor cells. In conclusion, there are various lines of evidence that antigen-induced cell death contributes to the regulation of cellular immune responses as well as to the establishment of peripheral immune tolerance. The continued elucidation of the molecular mechanisms involved in the control of AICD will hopefully provide exciting perspectives for the treatment of certain diseases.