A historical perspective on immunological privilege.

Intimations of immunological privilege in sites of the body such as the eye and the brain go back in the literature more than a century, to reports of experiments using outbred animals and tumor transplants. The starting points of this review, however, are publications stemming from the transplantation of normal tissues and, as far as possible, the use of inbred animals, exploring the way in which interplay between genetic differences of different degree, from single minor histocompatibility antigens to full-house major histocompatibility complex mismatches, has been reported to affect the 'take' of grafts in putatively privileged sites. While these sites traditionally included the brain, the eye, the pregnancy, and the endocrine tissues such as thyroid, parathyroid, adrenal, and islets of Langerhans, from readings of the literature, it is clear that the eye and the pregnancy have claims to being in the strongest positions of privilege. Even then, the position is precarious, with stirrings of the adaptive immune system poised to attack. Various regulatory mechanisms have now moved center stage and will undoubtedly form a significant part in subsequent chapters in this volume. Perhaps surprisingly, as investigations on these mechanisms have advanced, there is evidence for the convergence of those mechanisms controlling both induced tolerance and immunological privilege.