CD154 for the dragon: a promising development for pancreatic islet transplantation and cure for type 1 diabetes mellitus.

Abstract

Zeus looked down from the top of Mount Olympus and laid his eyes on Thurma, the beautiful princess of the small island kingdom of Styconos in the Aegean Sea. Smitten with desire, he instantly transformed himself into a white dove and flew down to win her affections. Thurma, delighted and utterly charmed by the sweet bird, easily succumbed to the god and soon thereafter found herself pregnant with a child. Hera, Zeus’ sister and first wife had been watching, and, in her jealousy, had turned the son into a dragon while he was still in the womb of his mother. In her rage, Hera devised that the monster would grow evil and turn against the people of the kingdom. Meanwhile the King had received an oracle prophesying that his kingdom would be devastated by a dragon born from his daughter. Upon finding her pregnant, he immediately banished her to an isolated cave at the edge of the island, forbidding her to return until she had given birth and all was declared safe. Though she was visited daily by a royal attendant, Thurma was quite lonely in the dim light of the grotto, and spent countless hours singing to herself and her child. She sang of the pleasantries of the outside world, which she missed, as well as of the follies of famous heroes, and so, when her son was finally born among the shadows, while still dragon in form, his mind and spirit were gentle. Such was the King’s despair at birth of the first dragon prince ‐ seeing the fulfilment of the oracle ‐ he abandoned Styconos and left with the disheartened Queen on a rough sea never to return. But Thurma loved her childdragon Hesperon (whose name means the son of a god and a beautiful princess), who at birth was so beautiful and gentle that the people of the island took him into their hearts. Even jealous Hera, who had come to see the fate of the island, was taken by Hesperon’s looks. She regretted what she had done and took the evil spirit from the dragon so that now he would not harm the people of the island but protect them from intruders. Hesperon would catch an intruder but do him no further harm unless the people of the island signalled that they did not recognize the intruder as friendly. Then only would Hesperon devour the intruder. We find the myth of the dragon Hesperon reflected in our present understanding of how the immune system distinguishes self (native) from non-self (intruder). Knowledge of how the immune system is kept from turning against itself has allowed the induction of specific tolerance even towards transplanted tissue. This Highlight summarizes the pertinent molecular mechanisms involved in the discrimination of self and non-self by the immune system and outlines exciting new studies in transplant tolerance. Until the mid-1960s it was thought that the immune system discriminated between self molecules and those belonging to pathogens by deleting all self-reactive