[The CD95/CD95L system as target for modulation of allogeneic immune responses]

The effects of COS7 cells which constitutively express the apoptosis-inducing human CD95 ligand (COSh95L cells) on in vitro alloimmune responses were investigated. In the presence of COSh95L cells a clear-cut inhibition of alloantigen-induced proliferation was observed. In these cultures fully activated blastoid T cells were absent suggesting that deletion of activated T cells is one mechanism of COSh95L-mediated inhibition of proliferation. Non-fully activated cells were not eliminated in MLR by COSh95L cells but achieved a hyporesponsive state as shown by their failure to proliferate in response to restimulation with alloantigen or mitogen. These data indicate that the effects of CD95L on T cells are heterogeneous. Further analysis of the actions of CD95L in T cells of different activation states and subsets will be crucial to estimate the therapeutical potential of this molecule as target for immunomodulation after allo- and xenotransplantation.