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The Study of Immune Tolerance by CD40-mAb Blockading CD40-CD40L Interaction in Guinea-pig to Rat Heart Transplantation

Author: ZhangWeiMin
Tutor: ShenZhenYa
School: Suzhou University
Course: Thoracic and Cardiovascular Surgery
Keywords: heart xenotransplantation immune tolerance CD40LmAb mixed lymphocyte reactior
CLC: R654.2
Type: Master's thesis
Year: 2004
Downloads: 65
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Abstract


Introduction: Xenotransplantation is the bes: way to solve the problem of donor absence, but its development is barreled by the xenograft rejection.This study was designed to investigate the effect of T cells on the delayed xenograft rejection by CD40L-mAb blockading CD40/CD40L interaction-the most important stimulatory molecules, and to investigate the possibility of inducing the immune tolerance to heart xenograft by the way of T cells. Materials and methods: In this experiment, guinea-pig and SD rat were , respectively, selected as donor and recipient. A model of rat heterotopic heart xenograft was established by using Ono’stechnique. Experimental animals were divided randomly into three groups: 1.the blank group(group A):recipients accept heart transplantation without pretreatments;2.the contronl group(group B):recipients were trea:ed with CVF by intraperitoneal injection at the dose of 0.4mg/kg on 20-24 hours before transplantation.3.the CD40-mAb group(group C):recipients were treated with CD40L-mAb by intraperitoneal injection at the dose of 100ug before transplantation,the other pretreatments were the same as group B.In order to observe the survival time of cardiac xenograft , the heart beating was palmed in rat’s abdomen.The mixed lymphocyte reaction with [3H] trymidine for 24 hours beforeharvesting was used to inspect the CD40L-mAb blockading costimulatory molecules in vivro,the CPM(counts per minute)were measured .The changes of IL-4, IFN-- Y were detected with the ELISA after transplantation. Results:1. In heart xenotransplantation group, Survival time of donor heart in group B(l 7.2+1. 9h),group C(24.5+l.lh) were significantly longer than group A(0.4+0.1)(p<0.01);group C was longer than group B(p<0.05). the graft survival time prolonged significantly (p<0.01). 2.The results of MLR(mixed lymphocyte reaction)showed that the stimulative effect in group C(2556+220) were less active than that in group A(3532+469) and group 6(3553+386) (p<0.01).but there were no evident difference between group A and group B (p>0.05) .3. There was no significantly discrepancy of IL-4 in group A(2463 74pg/ml)and B(2414 69pg/ml). The IL-4 in group C(3545 + 122 pg/ml) was significantly higher than group A and group B after transplantation(p<0.05) 0There were no significantly discrepancies of IFN- Y in group A(789 54 pg/ml) and B(773 59 pg/ml). The IL-4 in group C(467 45 pg/ml) was significantly lower than group A and group B after transplantation(p<0.05) ?Conclusions:l.CVF is beneficial to overcome the hyperacute rejection. 2.CD40L-mAb can partly inhibited the activating ’of T lymphocytes in vitro.3.CD40L-mAb can prolong the survival of the donor heart. The blockade CD40-CD40L interaction can induce rat heterotopic xeno-heart allograft immune tolerance. It may provide a new way to treat immune rejection to xenotransplantation.4 CD40LmAb can induce THICK into TH2CK,and contribute to immune deviation and immune tolerance.

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