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Inactivation of host mature T cells in induction of immune tolerance at early stage after transplantation

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Author:
LI Zeng-qi(Department of Cardiovascular Surgery, First Affiliated Hospital, Fujian Medical University Fuzhou 350004, China)
CHEN Yang-tian(Department of Cardiovascular Surgery, First Affiliated Hospital, Fujian Medical University Fuzhou 350004, China)
CHEN Jia-song(Department of Cardiovascular Surgery, First Affiliated Hospital, Fujian Medical University Fuzhou 350004, China)
LIAO Dong-shan(Department of Cardiovascular Surgery, First Affiliated Hospital, Fujian Medical University Fuzhou 350004, China)
Journal Title:
CHINA MEDICINE
Issue:
Volume 3, Issue 06, 2008
DOI:
Key Word:
Allogeneic heart transplantation; Non-myeloablative bone marrow transplantation; Immune tolerance

Abstract: Objective To observe the role of immune cells which possibly leads to failure of nonmyeloablative immune tolerance in acute rejection at the early stage after bone marrow transplantation. Methods BALB/c (WT) recipients were divided into three groups which were conditioned respectively with TBI (800 cGy) +BMT, TBI(450cGy) + BMT, ATS + TBI (450cGy) + BMT. Chimera was examined respectively in peripheral blood, spleen, thymus of the hosts 7,14,21,28,42 days after bone marrow transplantation (BMT). Recipients,C 57 BL/6 TCRα-KO and wild-type C 57 BL/6, were treated by the same conditioning regimen[TBI (450cGy) +BMT], and then were performed heart transplantation from BALB/C donor. We evaluated the important role of host mature T cells in acute rejection and induction of immune tolerance. Results In TBI(450cGy) + BMT group, some host T cells still survived in peripheral blood and spleen (respectively 0.23% and 0.48% of the whole white blood cells) and a lot of host cells survived in Thymus (99%) on the 7th day after BMT. All the heat allografts in this group had rejection within 38 days after heart transplantation. In TBI (800 cGy) + BMT and ATS + TBI(450cGy) +BMT groups, very few host T cells survived in peripheral blood and spleen (respectively 0.02%, 0.05% and 0.01% ,0.05% ) and chimeric index of donor cells was 30% in the host thymus on 7th day after BMT. Most of heart allografts in these groups didn t have rejection. All C 57 BL/6 TCRα-KO hosts treated by TBI(450cGy) + BMT regimen accepted allogeneic heart grafts (graft survival time > 100 days) and got complete chimera of donor cells ( chimeric index 99.4% ). Conclusion Depletion or dysfunction of anti-donor-antigen host mature T cells at early stage of transplantation not only prevented acute rejection, but also contributed to donor bone marrow cell engraftment and creation of stable chimerism that produced central immunologic cell clonal deletion and induced long-term specific immune tolerance. It is important to set up non-myeloablative conditioning regimen in clinical transplantation.

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