In this issue, O'Connell et al. suggest that Fas ligand (FasL) mediates immune privilege by protecting tumors or tissues from immune attack, but we maintain that there is no convincing evidence of this. We would also like to re-emphasize our views of FasL: contrary to the suggestion of O'Connell and colleagues, we do not regard FasL as “solely a mediator of inflammation”, but instead, find that Fas and its ligand are involved in target cell killing and immune cell homeostasis, especially as mediators of activation induced cell death in T-cells 2. Although there can be differences of opinion, there are a number of important studies omitted from this commentary crucial to the interpretation of evidence supporting the'FasL counterattack'hypothesis 1.

We caution against any dismissal of concerns about scientific methods and reagents 1. Faulty reagents have been and continue to be a significant source of error 2. The antibodies used in many studies have been clearly shown to lack specificity 3. This is especially the case for the monoclonal antibody mAb33 from Transduction Labs, which stains CD95L-transfected and untransfected cells to a similar extent, labels tissue sections that lack CD95L mRNA and stains a protein by 2D-electrophoresis with a different mobility than FasL. A similar lack of specificity has been observed for both the C-20 and N-20 antibodies from Santa Cruz Biotechnology. The validity of functional assays, especially those using Jurkat cell death, have been challenged by others 4.