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T-Cell-Based Immunosuppressive Therapy Inhibits the Development of Natural Antibodies in Infant Baboons

  作者 Dons, EM; Montoya, C; Long, CE; Hara, H; Echeverri, GJ; Ekser, B; Ezzelarab, C; Medellin, DR; van der Windt, DJ; Murase, N; Rigatti, LH; Wagner, R; Wolf, RF; Ezzelarab, M; West, LJ; Ijzermans, JNM; Cooper, DKC  
  选自 期刊  Transplantation;  卷期  2012年93-8;  页码  769-776  
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[摘要]Background. We set out to determine whether B-cell tolerance to A/B-incompatible alloantigens and pig xenoantigens could be achieved in infant baboons. Methods. Artery patch grafts were implanted in the abdominal aorta in 3-month-old baboons using A/B-incompatible (AB-I) allografts or wild-type pig xenografts (pig). Group 1 (Gp1) (controls, n = 6) received no immunosuppressive therapy (IS) and no graft. Gp2 (n = 2) received an AB-I or pig graft but no IS. Gp3 received AB-I grafts + IS (Gp3A: n = 2) or pig grafts + IS (Gp3B: n = 2). IS consisted of ATG, anti-CD154mAb, and mycophenolate mofetil until age 8 to 12 months. Gp4 (n = 2) received IS only but no graft. Results. In Gp1, anti-A/B and cytotoxic anti-pig immunoglobulin-M increased steadily during the first year. Gp2 became sensitized to donor-specific AB-I or pig antigens within 2 weeks. Gp3 and Gp4 infants that received anti-CD154mAb made no or minimal anti-A/B and anti-pig antibodies while receiving IS. Discussion. The production of natural anti-A/B and anti-pig antibodies was inhibited by IS with anti-CD154mAb, even in the absence of an allograft or xenograft, suggesting that natural antibodies may not be entirely T-cell independent. These data are in contrast to clinical experience with AB-I allotransplantation in infants, who cease producing only donor-specific antibodies.

 
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