Paternal Cell Immunization Raises Autoantibodies and Improves Pregnancy Success in Mice Igor Barjaktarevic, Stanislav Vukmanovic Center for Cancer and Immunology Research, Children’s Research Institute, Children’s National Medical Center, Washington, DC, USA Introduction The fetus represents foreign entity to the maternal immune system. Despite the plethora of paternal antigens expressed by the fetus, the maternal immune system does not reject fetus, at least not in the successful pregnancies. However, the absence of rejection does not mean that the mater- nal immune system ignores the paternal antigens. Rather, a number of regulatory mechanisms aimed at preventing the rejection of the fetal allograft have been put in place by the immune system. 1 Failure of one of those mechanisms, such as try- ptofan catabolism or regulatory T cells, is sufficient to result in pregnancy failure. 2,3 It is therefore not surprising that immunological mechanisms are thought to form the bases of at least a subset of human recurrent miscarriages. 4 Paternal cell immu- nization is a relatively frequently used form of ther- apy of recurrent miscarriage, 4 thought to induce tolerance to paternal antigens, in the same way as transfusion given before transplantation decreases rejection of organ allografts. 5,6 Despite frequent claims to its success, 7–9 the efficacy of the paternal cell immunization therapy has been questioned. 10 Relatively little experimental data exist on the effects of paternal cell immunization on pregnancy success, which could help us to understand the underlying mechanisms of immune-based miscar- riage and of the efficacy of cellular immuno- therapy. To determine the extent to which immunity to paternal antigens can lead to preg- nancy failure, we immunized female mice with male spleen cells prior to mating. Keywords Autoimmunity, cell therapy, paternal antigens, pregnancy Correspondence Stanislav Vukmanovic, Center for Cancer and Immunology Research, Children’s Research Institute, Children’s National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA. E-mail: svukmano@cnmc.org Submitted May 6, 2008; accepted July 7, 2008. Citation Barjaktarevic I, Vukmanovic S. Paternal cell immunization raises autoantibodies and improves pregnancy success in mice. Am J Reprod Immunol 2008; 60: 497–500 doi:10.1111/j.1600-0897.2008.00646.x Problem Autoimmunity and alloimmunity are thought to be the bases of some recurrent miscarriages. Paternal cell immunization was used with varying success as the treatment of allo-immune-mediated recurrent miscarriages. Method of study Female mice immunized with paternal cells were assessed for develop- ment of male-specific antibodies and autoantibodies. Pregnancy success rates were compared between immunized and control mice. Results The immunization with male cells resulted in an increase in the number of successful pregnancies without affecting the size of the litter. Surpris- ingly, paternal cell injections before the pregnancy induced mostly autoantibodies, rather than male-specific antibodies. Conclusion These findings suggest that autoantibodies may have a protective, rather than damaging role in promoting pregnancy. ORIGINAL ARTICLE American Journal of Reproductive Immunology 60 (2008) 497–500 ª 2008 The Authors Journal compilation ª 2008 Blackwell Munksgaard 497