Accommodation and the Fetus
The mammalian fetus usually expresses major histocompatibility antigens not present in the mother. Such incompatibility of major histocompatibility antigens between “ordinary” grafts and the recipient provokes a powerful immune response and rejection of t
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Accommodation and the Fetus Ines Silva, Cody A. Koch, Raymond J. Lynch, and Jeffrey L. Platt
Introduction The term “accommodation” refers to acquired resistance of a graft to injury by the immune system of the recipient of that graft. Accommodation was “discovered” in the 1980s as an explanation for the unanticipated survival and well-being of organs transplanted across ABO blood group barriers (blood group A or B organs expressing blood group A or B transplanted into recipients producing antibodies against one or both of those blood groups) [7, 15]. Organs transplanted across blood group barriers usually undergo early and severe rejection; approximately 75 % fail within 3 months [52]. However, if anti-blood group antibodies are removed from recipients or the binding of these antibodies is blocked, the prospects for long-term survival and function of the graft approach that of grafts matched for ABO blood groups [1]. Although several explanations I. Silva • R.J. Lynch Departments of Surgery, University of Michigan, Ann Arbor, MI, USA C.A. Koch Department of Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA J.L. Platt, M.D. (*) Departments of Surgery, University of Michigan, Ann Arbor, MI, USA Department Microbiology and Immunology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA e-mail: [email protected]
including spontaneous tolerance [24] and loss of the antigenic target [2] might explain this phenomenon, the organs were found to persist in expression of antigen, and the recipients were found to continue to produce anti-blood group antibodies [7, 15]. These findings led to the suggestion that the organ might have changed in some way that would allow it to “accommodate” to what would otherwise be a toxic assault by antibodies of the recipient and activation of complement [42]. In this communication, we discuss the possibility, yet theoretical, that accommodation may explain the survival of the fetus as an allograft.
Mechanisms Underlying Accommodation Accommodation of organ transplants may involve one or more of three mechanisms of resistance. Accommodation may reflect heightened control of complement activation such that sub-toxic rather than toxic amounts of complement are activated upon binding of anti-graft antibodies. Dalmasso et al. [21] showed that activation of complement on endothelial cells heightens expression of CD59, which inhibits killing of cells by terminal complement complexes. Williams et al. [53] showed that for a given amount of antibody binding, accommodated organs activate less complement than rejecting organs, and this decrease reflects control of complement at
N. Bhattacharya, P. Stubblefield (eds.), Human Fetal Tissue Transplantation, DOI 10.1007/978-1-4471-4171-6_6, © Springer-Verlag London 2013
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the level of C3 or C4. Koch et al. [28] showed that hepatocytes, which, like accommodated organs, resist complement-mediated killing, also exhibit intrinsic inhibition at the level of C3 or C4. Accommodation may result from changes
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