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KMID : 0371319840260030281
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Journal of the Korean Surgical Society
1984 Volume.26 No. 3 p.281 ~ p.289
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Cardiac Allograft Survival by Pretreatment of Donor Rats with Anit-B Lymphocyte Antibody
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김응국/Kim, Eung Kook
김승남/고용복/강래성/이용각/Kim, Seung Nam/Koh, Yong Bok/Kang, Rae Sung/Lee, Yong Kak
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Abstract
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In spite of numerous efforts, the major problem in organ transplantation, rejection reaction, remains unsolved. The immunosuppressive modalities to combat rejection are also not so improved than belore that conventional immunosuppressants, Azathioprine and steroid have to be utilized to treat recipient at most transplantation conters.
Close attention should be paid while using these immunosuppressive drugs because unexpected complication can occur and insult the recipient seriously.
Recently, several reports suggested that successful immunosuppression can be achieved by donor or donor organ pretreatment instead of recipient treatment(Russel & Cosimi, 1979; Brent & Hutchinson, 1981).
They pointed out that the passenger leukocytes, carried in donor organ, play the most important role and Ia antigen on their surface initiates rejection reaction in the host(Elkins & Guttmann, 1968; Lacy et al., 1978 a).
In laboratory works, concerning donor pretreatment, Faustman et al. (1981, 1982) reported successful cell or tissue transplantation by culture with anti-Ia antibody at 37℃ but application of this model to whole organ transplantation is difficult because the organ cannot endure the long warm ischemic time.
The author´s experiment was undertaken using rat heart transplantation model to investigate the possibility that Ia antigen on donor rat heart could be reduced by systemic perfusion with antibody in specially prepared donor instead of in vitro culture.
Rabbit anti-rat B lymphocyte antiserum was obtained by weekly injection of 2×l0 splenic B lymphocyte intraperitoneally for 6 weeks.
Sprague Dawley was used as donor and Spontaneously Hypertensive Rat was used as recipient rat. The donor rats were prepared with 640 R whole body irradiation except for heart 3 days prior to transplantation and 0.2 ml of anti-B lymphocyte antiserum diluted 1:10 (titer, 1: 1024) was given intravenously, 2 hours prior to transplantation.
The experimental rats were divided into 3 groups according to the pretreatment method of donor rats; as no pretreatment group(NR group), 640 R irradiation group(R group) and 640 R irradiation and anti-B lymphocyte injection group(R. Ab group).
The graft heart survival was determined by daily palpation and serial ECG tracing. The beating graft heart was excised periodically to examine pathological changes and to compare the grafts in each experimental groups.
The experimental results were as follows;
1) Effective, specific anti-B lymphocyte antiserum could be obtained by repeated injection of rat splenic B lynphocytes into the rabbit peritoneal Cavity. Even 1 :1024 dilution, antiserum had the cytolytic activity of 50% of rat B lymphocytes.
2) Considerable decrease of total leukocyte count with almost absence of lymphocytes was found in all the donor rats on 3rd postirradiation of 640 R.
3) The graft heart from the donor pretreatment with irradiation and anti-B lymphocyte antiserum kept beating considerably longer(18. 6±2.2 days) than only irradiation group (7. 9±1.6 days) and not pretreated group(4.9±o.7 days) (p<0.01).
4) Comparing the pathological changes of graft hearts at the same post-transplantation day in each experimental rats. The findings of rejection were less severe and slowly progressed in R.Ab groups
With the above results, the author observed that pretreatment of donor heart with anti-B lymphocyte antibody prolonged allograft survival in rats. The authors´ experiment suggested that donor or donor organ pretreatment with anti-Ia antibody could be applied in clinical cadaveric organ transplantation if the safe and potent antibody for human would be manufactured.
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