PRECLINICAL STUDIES OF ALLOGRAFT TOLERANCE IN RHESUS MONKEYSA Novel Anti-CD3-Immunotoxin Given Peritransplant with Donor Bone Marrow Induces Operational Tolerance to Kidney Allografts1
作者:
Thomas2,3,
Judith Neville4,
David Contreras2,
Juan Eckhoff2,
Devin Meng2,
Gang Lobashevsky2,
Andrew Wang2,
Pei Huang2,
Zhi Verbanac5,
Kathryn Haisch5,
Carl Thomas2,
期刊:
Transplantation
(OVID Available online 1997)
卷期:
Volume 64,
issue 1
页码: 124-135
ISSN:0041-1337
年代: 1997
出版商: OVID
数据来源: OVID
摘要:
A major challenge in clinical transplantation today is to design a practical and effective protocol for tolerance induction compatible with cadaver organ transplantation. A preclinical rhesus monkey kidney allograft model using immediate peritransplant anti-CD3 immunotoxin (anti-CD3-IT) and donor bone marrow (DBM) is shown here to induce operational tolerance with prolonged graft survival in the absence of chronic immunosuppressive drugs. Bone marrow harvested from the kidney donor was depleted of mature alloantigen-presenting cells and T cells by removing DRbrightcells and CD3brightcells, respectively. In out-bred, major histocompatibility complex-incompatible donor-recipient pairs with high pretransplant mixed lymphocyte response and cytotoxic T lymphocyte precursor activity, four of six allografts survived for periods of 120 days to >1.5 years. Graft acceptance after peritransplant treatment followed robust elimination of both peripheral blood T cells and lymph node T cells. In most recipients given anti-CD3-IT and DBM infusion, anti-donor immunoglobulin G responses were completely inhibited. Microchimerism was observed in all recipients studied, including those not given DBM, but levels of microchimerism did not cor-relate with graft survival. Anti-CD3-IT induction in combination with modified DBM protocols such as the depletion of mature T cells and DRbrightantigen-presenting cells may offer new opportunities to improve clinical tolerance protocols beyond those attempted in the clinic to date. Overall, these results with anti-CD3-IT show promise for development of cadaver transplant tolerance induction.
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