| Objective Post-transplant lymphoproliferative disorder, which is rare, develop post the transplantation of entity organ or marrow. It contains active plasma cell proliferation, malignant lymphoma and so on. It is one kind of the immunologic deficit lymphoproliferative disease.There are many differencies in morphous,clinic, treatment and prognosis in comparison with lymphoproliferative disease from the health adults. With the fast development of organ transplantation, the incidence of PTLD grows rapidly. It is well investigated abroad,but the associated reports are rare in the domestic, except for some individual cases.The aim of this thesis is to establish the animal model in the SCID,and probe the rate of the mode establishment, which is based on to study the relationship between TGF-βand PTLD. And it provide a platform, on which we can deeply study the pathogenesy and clinical diagnosis and treatment of PTLD.Methods The SCID mice are utilized to imitate the environment of immune defect or immune suppression ,and the EBV from human are utilized to imitate the environment of EBV infection.Then we explore the relationgship of TGF-βand PTLD through the comparison of monoclonal antibody and PBS.TGF-β. EBV(+)huPBL were isolated from peripheral blood of healthy donors and intraperitoneally injected into SCID mice. IgG determination was utilized to confirm the reestablishment of human immunocell in SCID mice. Take out the tumor tissue of the mice after dying, and then ascertain its B cell origin by pathological section and immunohistochemistry. Then pick out those volunteers whose EBV(+) huPBLs are easyer to develop LPD in SCID mice, and repeat the lab proc above-mentioned to establish another group of EBV(+)huPBL-SCID model. At last, separate those SCIDs into experimental group(injected with anti-TGF-β) and control group(injected with PBS)to study the research of survival analysis and LPD detection.Results The IgG level in the blood serum of SCIDmice are (750.0±13.2)μg/ml and (1050.0±14.6)μg/ml respectively 8 weeks and 12 weeks post transplantation. Take out the tumor tissue of the mice after dying. Pathological section indicates that the tissue is large-cell lymphoma with high mitotic rates.The tumors are CD20 positive and LMP-1 positive.There is heterogeneity in LPD development in hu-PBL-SCID mice among donors;In the reestablished EBV(+)huPBL-SCID models, Of all of the 40 volunteers, human peripheral blood lymphocyte from 10 volunteers (25%) produce LPD rapidly(median time to LPD, 8 weeks)and with high penetrance (median, 100%),whereas 20% (8 of 40) developed LPD tumor later (median 12 weeks), and in fewer mice (median penetrance, 55%).HuPBLs from the remainder of the donors(22 of 40,55%) produced no LPD after 16 weeks. There are many differences between experimental groups and control groups, such as survival time (t= 35.78, P<0.05) , LPD incidence (P=0.003<0.01) as well as the distribution of the T and B cells in tumors. And the differences in latency and penetrance between the rapid and late groups are statistically significant.Conclusion 1 .PTLD modle can be successfully established by intraperitoneal injection of EBV(+)huPBL in SCID mice2.TGF-βmay contribute to the onset of post-transplant lymphoproliferative disorder,and the character of TGF-βis responsible for it.
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