Prolongation of Rat Major Histocompatibility Complex-compatible Cardiac Allograft Survival During Pregnancy

Background: it has been suggested that pregnancy-related hormones play a critical role in mediating selective immune tolerance during pregnancy. An understanding of why a woman's body normally does not reject the fetus is highly relevant to the prevention of transplant rejection. Methods: The hearts of female inbred F344 rats (RT-1(lvl)) were transplanted into naive Lewis (RT-1(l); nLewis) or pregnant (pLewis; Day 6, 12 and 18 of pregnancy) rats. The mean survival time (MST) of the cardiac allografts between the nLewis and pLewis rats was compared. We determined the rate. of proliferation of the T cells isolated from nLewis and pLewis rats in response to concanavalin A (ConA), anti-CD3 and -CD28 antibody and alloantigen stimulation ex vivo. mRNA expression of several cytokines in these T cells was analyzed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the effect of estriol on the cardiac allograft was tested. Results: The pLewis rats with transplant on Day 12 of pregnancy had the most significantly prolonged F344 cardiac graft survival (MST 13.3 days) as compared with nLewis recipients (MST 8 days). pLewis T-cell proliferation was stimulated by alloantigen and antibody but ConA was reduced, whereas,Th1/Th2 cytokine mRNA profiles in the T cells were similar for nLewis and pLewis rats. Likewise, estriol also significantly prolonged survival of cardiac allografts. Conclusions: The results of this study demonstrate that pregnancy hormones not only appear to play a critical role in maternal acceptance of the fetus, but also have therapeutic potential for prolonging the survival of major histocompatibility complex (MHC)-compatible allografts during pregnancy. J Heart Lung Transplant 2009;28:176-82. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation.