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.
BACKGROUND: We set out to determine whether B-cell tolerance to A/B-incompatible alloantigens and pig xenoantigens could be achieved in infantbaboons. 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 Gp4infants 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.
Authors: B J Holmes; A Richards; M McLaughlin; G Cruz; L Copeman; S Bycroft; H Schuurman; D J White; H Davies; E Cozzi Journal: Transplant Proc Date: 2001 Feb-Mar Impact factor: 1.066
Authors: L J West; S M Pollock-Barziv; A I Dipchand; K J Lee; C J Cardella; L N Benson; I M Rebeyka; J G Coles Journal: N Engl J Med Date: 2001-03-15 Impact factor: 91.245
Authors: Carol J Phelps; Chihiro Koike; Todd D Vaught; Jeremy Boone; Kevin D Wells; Shu-Hung Chen; Suyapa Ball; Susan M Specht; Irina A Polejaeva; Jeff A Monahan; Pete M Jobst; Sugandha B Sharma; Ashley E Lamborn; Amy S Garst; Marilyn Moore; Anthony J Demetris; William A Rudert; Rita Bottino; Suzanne Bertera; Massimo Trucco; Thomas E Starzl; Yifan Dai; David L Ayares Journal: Science Date: 2002-12-19 Impact factor: 47.728
Authors: Bruce E Loveland; Julie Milland; Peter Kyriakou; Bruce R Thorley; Dale Christiansen; Marc B Lanteri; Mark Regensburg; Maureen Duffield; Andrew J French; Lindsay Williams; Louise Baker; Malcolm R Brandon; Pei-Xiang Xing; Del Kahn; Ian F C McKenzie Journal: Xenotransplantation Date: 2004-03 Impact factor: 3.907
Authors: Hidetaka Hara; Andrew Bentall; Cassandra Long; Jason Fang; Oleg Andreyev; John Lunz; Mohamed Ezzelarab; Kareem M Abu-Elmagd; Ron Shapiro; David Ayares; Mark Stegall; David K C Cooper Journal: Xenotransplantation Date: 2013-09-03 Impact factor: 3.907
Authors: Whayoung Lee; Hidetaka Hara; Mohamed B Ezzelarab; Hayato Iwase; Rita Bottino; Cassandra Long; Jagdeece Ramsoondar; David Ayares; David K C Cooper Journal: Xenotransplantation Date: 2016-03-14 Impact factor: 3.907
Authors: Huidong Zhou; Hayato Iwase; Roman F Wolf; Burcin Ekser; Mohamed Ezzelarab; Hidetaka Hara; Gary White; David K C Cooper Journal: Xenotransplantation Date: 2014-02-18 Impact factor: 3.907
Authors: Mohamed Bikhet; Mahmoud Morsi; Hidetaka Hara; Leslie A Rhodes; Waldemar F Carlo; David Cleveland; David K C Cooper; Hayato Iwase Journal: Pediatr Transplant Date: 2020-08-26