Details

Autor(en) / Beteiligte

• Dons, Eefje M
• Montoya, Claudia
• Long, Cassandra E
• Hara, Hidetaka
• Echeverri, Gabriel J
• Ekser, Burcin
• Ezzelarab, Corin
• Medellin, Dasha Roa
• van der Windt, Dirk J
• Murase, Noriko
• Rigatti, Lora H
• Wagner, Robert
• Wolf, Roman F
• Ezzelarab, Mohamed
• West, Lori J
• Ijzermans, Jan N M
• Cooper, David K C

Titel

T-cell-based immunosuppressive therapy inhibits the development of natural antibodies in infant baboons

Ist Teil von

• Transplantation, 2012-04, Vol.93 (8), p.769-776

Ort / Verlag

United States

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• We set out to determine whether B-cell tolerance to A/B-incompatible alloantigens and pig xenoantigens could be achieved in infant baboons. 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. 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. 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.