Tcell anergy and peripheral Tcell tolerance

The discovery that Tcell recognition of antigen can have distinct outcomes has advanced understanding of peripheral Tcell tolerance, and opened up new possibilities in immunotherapy. Anergy is one such outcome, and results from partial Tcell activation. This can arise either due to subtle alteration of the antigen, leading to a loweraffinity cognate interaction, or due to a lack of adequate costimulation. The signalling defects in anergic T cells are partially defined, and suggest that Tcell receptor (TCR) proximal, as well as downstream defects negatively regulate the anergic T cell's ability to be activated. Most importantly, the use of TCRtransgenic mice has provided compelling evidence that anergy is an in vivo phenomenon, and not merely an in vitro artefact. These findings raise the question as to whether anergic T cells have any biological function. Studies in rodents and in man suggest that anergic T cells acquire regulatory properties; the regulatory effects of anergic T cells require cell to cell...