INTRODUCTION: Although transplantation of an allo-graft normally induces immune activation resulting in graft rejection, it is possible to activate a state of immune tolerance to the graft by a brief period of therapy. Once established, this tolerance is self-sustaining.
AIM: We have explored the molecular basis by which the immune response is regulated between tolerance and rejection using an ex vivo model, comparing spleen cells from graft-tolerant CBA mice, to those from graft-rejected CBA mice.
RESULTS: The main characteristics of the tolerant response were (i) a low INF-gamma response; (ii) increased levels of signal transducer and activator of transcription 3; (iii) increased levels of c-kit, the receptor for stem cell factor; and (iv) accumulation of leukaemia inhibitory factor. Full length c-kit became transiently localised within the nucleus at 48h in both the tolerant and rejection responses.
CONCLUSION: We conclude that signalling pathways that are central to stem cell control appear also to be involved in the regulation of immune tolerance. |