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发表于 2004-3-27 23:18
4)Ilan Y, Nagler A, Adler R, Tur-Kaspa R, Slavin S, Shouval D.Ablation of persistent hepatitis B by bone marrow transplantation from a hepatitis B-immune donor.Gastroenterology 1993 Jun;104(6):1818-21
Chronic hepatitis B virus (HBV) infection is still a major cause of liver disease for which no definite therapy is available. We describe here a hepatitis B surface antigen (HBsAg) carrier patient with active viral replication (HBV DNA positive) who was treated for leukemia by bone marrow transplantation (BMT) from an HBV immune donor. Following BMT from the antibody to hepatitis B core antigen (anti-HBc) positive/anti-HBs positive bone marrow donor, immune reconstitution of the recipient's bone marrow resulted in clearance of the circulating HBsAg, as well as HBV DNA. The patient acquired immunity against HBV, which lasted for more than 8 months posttransplantation. Therefore, this report provides evidence that adoptive transfer of specific immunity against HBV through allogeneic BMT may lead to clearance of persistent HBV infection. Furthermore, the data support the hypothesis that the HBsAg carrier state is most probably the result of an inefficient immune response against HBV, implying that clearance of HBV may be facilitated by adoptive cellular immunotherapy.
采用天然HBV免疫的供体进行BMT可治愈慢性HBV感染受体的HBV感染,因此细胞过继免疫疗法是清除HBV感染有力手段
5)Shouval D, Adler R, Ilan Y. Adoptive transfer of immunity to hepatitis B virus in mice by bone marrow transplantation from immune donors.Hepatology 1993 Jun;17(6):955-9
Recipients of allogeneic bone marrow transplantation are immunosuppressed as a result of their primary disease and by myeloablative therapy. Such patients are dependent on multiple blood products and are at risk for hepatitis B virus infection. Active immunization against hepatitis B in the immediate pre- and post-transplant periods is ineffective, presumably because of decreased T cell-dependent B-cell responses. This study was designed to evaluate, in a mouse model system, the transfer of immunity against hepatitis B to bone marrow transplant recipients through immunization of bone marrow donors against hepatitis B before transplantation. Bone marrow donor BALB/c mice were immunized with a recombinant hepatitis B vaccine. Seroconversion to HBs antibody occurred within 4 wk of primary immunization, and antibody levels in treated donor mice rose above 300 mIU/ml after a single booster injection. Bone marrow recipient mice, conditioned by sublethal irradiation, were injected intravenously with bone marrow cells obtained from syngeneic HBs antibody-positive immune donors. Antibody was detected in 10% of bone marrow recipients within 30 days of transplantation and in 56% 1 mo after a booster injection that led to a secondary rise in HBs antibody. Adoptive transfer of immunity to hepatitis B also occurred after transplantation of T cell-depleted bone marrow cells from hepatitis B-immune donors, albeit at a lower HBs antibody level. These results indicate that immunity to hepatitis B can be transferred in mice by bone marrow transplantation from hepatitis B-immune donors to immunosuppressed recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
采用HBV免疫的供体/小鼠进行BMT细胞过继免疫,可致受体的抗HBS产生增加,且去除T细胞亦有一定作用,说明DC/APC和T细胞均、有益于抗HBS抗体的产生,说明DC--TH1-BLC轴对于抗病毒免疫体液免疫产生很重要
6)Ilan Y, Nagler A, Adler R, Naparstek E, Or R, Slavin S, Brautbar C, Shouval D. Adoptive transfer of immunity to hepatitis B virus after T cell-depleted allogeneic bone marrow transplantation. Hepatology 1993 Aug;18(2):246-52
Recipients of allogeneic bone marrow transplantation are pancytopenic for several weeks and immunosuppressed for many months as a result of myeloablative therapy required to eliminate the basic disease and to prevent allograft rejection. After bone marrow transplantation, these patients remain profoundly immunosuppressed by the chemotherapy and immunotherapy used as prophylaxis against graft-vs.-host disease, treatment of established disease or both. These patients are usually dependent on multiple blood products and are therefore at risk for hepatitis B virus infection, which may run a fulminant course. Active immunization against hepatitis B virus in the immediate pre-bone marrow transplantation and post-bone marrow transplantation periods was found to be ineffective, probably because of the absence of T cell-dependent B-cell responses, which persists for approximately 1 yr after bone marrow transplantation. We studied adoptive transfer of immunity to hepatitis B virus through bone marrow transplantation in two populations of patients. The first group (A) consisted of 12 pairs of BMT donors and recipients, in which all bone marrow donors were positive for antibodies to HBc and HBs as a result of previously acquired hepatitis B virus infection and resolution; all recipients were negative to antibodies to HBc and HBs. The second group (B) consisted of eight pairs of donors and recipients in which all the donors were actively immunized against hepatitis B virus before bone marrow transplantation; all recipients were negative for all hepatitis B virus markers. All bone marrow transplantation recipients were monitored for antibodies to hepatitis B virus antigens.(ABSTRACT TRUNCATED AT 250 WORDS)
采用HBV免疫的供体/小鼠进行BMT细胞过继免疫,可致受体的抗HBS产生增加,且去除T细胞亦有一定作用,说明DC/APC和T细胞均、有益于抗HBS抗体的产生,说明DC--TH1-BLC轴对于抗病毒免疫体液免疫产生很重要
7)Ilan Y, Nagler A, Shouval D, Ackerstein A, Or R, Kapelushnik J, Adler R, Slavin S. Development of antibodies to hepatitis B virus surface antigen in bone marrow transplant recipient following treatment with peripheral blood lymphocytes from immunized donors.Clin Exp Immunol 1994 Aug;97(2):299-302
Bone marrow transplantation (BMT) recipients are immunosuppressed and are at risk for contracting severe infections. Recently, adoptive transfer of immunity against hepatitis B virus (HBV) was documented in BMT recipients receiving bone marrow from 'naturally' HBV-infected individuals who recovered spontaneously, or those transplanted with bone marrow cells obtained from actively immunized donors. Furthermore, reconstitution of the immune system in a BMT recipient who was a hepatitis surface antigen (HBsAg)+/HBV DNA+ carrier with HBV immune bone marrow cells led to clearance of the replicating virus, presumably through adoptive cell-mediated immunotherapy. We report three cases of induction of immunity to HBV by selective adoptive transfer by i.v. injection of peripheral blood lymphocytes (PBL) obtained from BMT donors who were actively immunized against HBV after harvesting of bone marrow. All three BMT recipients developed anti-HBs antibodies. In one BMT case in whom antibodies to HBsAg developed following adoptive transfer of immune PBL, a mild booster effect was documented in the BMT recipient upon immunization with a recombinant hepatitis B vaccine. The two remaining patients lost their antibodies to HBsAg in association with relapse of leukaemia. This immune manipulation may open the door to evaluation of adoptive transfer of immunity to HBV through selective transplantation of HBV immune lymphocytes in selected patients such as those with persistent HBV infection, as well as liver transplant recipients who require protection of the graft against HBV re-infection.
HBV感染受体选择性过继已采用HBV疫苗主动免疫的供者/供体的外周血淋巴细胞(CD4+????)便可成功地治疗受体的HBV感染并产生抗HBV抗体,且因免疫不同功能状态而产生抗HBS抗体与否及消失与否,因此对受体的CD4+治疗或过继已采用HBV疫苗主动免疫的供者/供体的外周血淋巴细胞中CD4+可能是一法,而HBV疫苗尤常规疫苗似可作治疗性疫苗用????
8)Shouval D, Ilan Y.Immunization against hepatitis B through adoptive transfer of immunity. Intervirology 1995;38(1-2):41-6
Clearance of hepatitis B virus (HBV) infection requires an effective T-cell-dependent humoral response that is often defective in HBV carriers and in immunosuppressed patients. We have shown in mice and humans that bone marrow (BM)-derived memory cells, capable of producing antibodies to the HBV envelope and nucleocapsid antigens, are transferable from BM donors (BMD) to their recipients. BMD BALB/c mice were immunized with recombinant HBV surface antigen (HBsAg), and BM from anti-HBs-positive donors was transplanted to irradiated recipient mice, who seroconverted to anti-HBs within 30 days of bone marrow transplantation (BMT), and responded to booster vaccination. In a similar manner, 19/26 human BM recipients, who received their HLA-matched BM from BMDs immunized once with HBsAg, seroconverted within several weeks after BMT. Antibodies to observHBsAg were alsoed in 3 recipients of peripheral blood lymphocytes (PBL) obtained from HLA-matched immunized human donors. Finally, clearance of HBsAg and HBV DNA was observed in an HBsAg carrier with leukemia who received BMT from his HLA-matched anti-HBc+/anti-HBs+ brother. These results indicate that adoptive transfer of immunity to HBV may be achieved through immunization of BM or PBL donors against HBV.
采用过继已采用HBV疫苗主动免疫的供者/供体的外周血淋巴细胞或者接受天然HBV免疫的供体进行BMT,均致HBV感染者的HBS AG清除和抗HBS抗体产生
9)Nagler A, Ilan Y, Adler R, Or R, Naparstek E, Shouval D, Slavin S. Successful immunization of autologous bone marrow transplantation recipients against hepatitis B virus by active vaccination.Bone Marrow Transplant 1995 Mar;15(3):475-8
Patients undergoing autologous bone marrow transplantation (BMT) are severely immunosuppressed. These patients are exposed to various infections agents due to delayed and efficient reconstitution of their immune system. Forty-eight patients with hemato-oncological malignancies were immunized against hepatitis B virus (HBV) following autologous BMT. Twenty one were vaccinated more than 10 days before BMT, 17 on days 1-9 before and 10 day after BMT. Thirty three patients (68.7%) seroconverted within 40 days after autologous BMT after receiving one dose of the vaccine before autologous BMT with a relatively low level of anti-HBs, whereas in 11 no anti-HBV antibodies could be detected. Nineteen patients remained seropositive but in 11 the seroconversion was only transient no correlation was found between permanent or transient seroconversion and basic disease, conditioning regimens, post-transplant therapy, immunotherapy and day of vaccination in relation to autologous and day of vaccination in relation to autologous BMT. Active HBV immunization of patients with malignancy undergoing autologous BMT is feasible and levels of antibodies, although low, are above the conventional protective titers. Therefore active immunization of some patients may reduce hepatitis-related complications in the setting of autologous BMT.
自体BMT前主动HBV免疫接种有效于产生抗HBS抗体
10)Nagler A, Ilan Y, Varadi G, Kapelushnik J, Or R. In vivo CAMPATH-1 followed by T cell-depleted bone marrow transplantation: a potential new mode of therapy for hepatitis-associated severe aplastic anemia (SAA). Bone Marrow Transplant 1996 Aug;18(2):475-8
Bone marrow transplantation (BMT) has been previously reported as a successful mode of treatment for hepatitis B and associated severe aplastic anemia (SAA). Non-A, non-B, non-C hepatitis is one of the causes of SAA. The etiology of SAA caused by non-A, non-B, non-C hepatitis is unknown. There is evidence that the immune response and, specifically, T cells and monocytes have a major role in both HCV- and HBV-induced liver damage. The liver damage caused by non-A, non-B, non-C hepatitis may be associated with similar mechanisms. We describe an 8-year-old girl who developed SAA post-non-A, non-B, non-C hepatitis infection. She was treated by in vivo CAMPATH-1G antibodies followed by T cell depleted HLA-matched BMT and cyclosporin A, resulting in gradual improvement and almost normalization of liver function. We suggest that treatment with CAMPATH-1G followed by T cell-depleted BMT and cyclosporin A could be a novel mode of therapy for viral non-A, non-B, non-C hepatitis-induced liver damage and associated SAA.
连最简单的非病原特异性BMT细胞过继免疫便可治NANBNC性肝炎呢
11)Lau GK, Lok AS, Liang RH, Lai CL, Chiu EK, Lau YL, Lam SK.Clearance of hepatitis B surface antigen after bone marrow transplantation: role of adoptive immunity transfer. Hepatology 1997 Jun;25(6):1497-501
Adoptive immunity transfer has been reported to be effective in clearing chronic hepatitis B virus (HBV) infection. Two hundred twenty-six patients who received allogeneic bone marrow transplantation (BMT) between May 1990 and September 1995 were screened for hepatitis B markers. Twenty-one patients were hepatitis B surface antigen (HBsAg) positive before BMT. The median follow-up period was 20 months (range, 2-59 months). Two of these patients had sustained clearance of HBV infection after transplantation. Both patients were hepatitis B e antigen (HBeAg)-negative, hepatitis B e antibody (anti-HBe)-positive, and serum HBV DNA-negative (by dot-blot hybridization) before BMT. Both had a flare in the serum alanine transaminase (ALT) level around the time of HBsAg clearance. Sustained clearance of HBsAg was observed in 2 of the 5 patients who received hepatitis B surface antibody (anti-HBs)-positive marrow but in none of the 16 patients who received anti-HBs-negative marrow (P < .05). One additional patient who received anti-HBs-positive marrow had transient HBsAg seroconversion. Among the 18 patients who remained persistently HBsAg-positive after BMT, 3 had HBeAg seroconversion and 3 had reversion to HBeAg positivity. In this study, we found a significant association between clearance of HBV infection and anti-HBs-positive bone marrow donors. Adoptive immunity transfer is effective in clearing HBV from patients with chronic HBV infection.
BMT中,HBV清除与 anti-HBs阳性BMT供体有关,因此采用天然HBV免疫的供体进行BMT通过过继免疫而治愈HBV感染
12)Ilan Y, Gabay E, Amit G, Feder R, Galun E, Adler R, Shouval D. Suppression of human hepatoma in mice through adoptive transfer of immunity to the hepatitis B surface antigen. J Hepatol 1997 Jul;27(1):170-5
BACKGROUND/AIMS: Adoptive transfer of immunity against hepatitis B surface antigen (HBsAg) has previously been shown to occur in mice and humans through transplantation of bone marrow cells from donors immunized against HBsAg (anti-HBs) to non-immune recipients. In the present study we evaluated the effect of adoptive transfer of immunity to HBsAg on the growth of HbsAg-secreting hepatocellular carcinoma (HCC) xenografts in athymic mice. METHODS: Immunocompetent mice were immunized with recombinant HBsAg. Bone marrow cells from anti-HBs+ mice were injected intravenously to irradiated athymic Balb/c mice which had been previously transplanted subcutaneously with Hep3B human hepatoma cells. Treatment groups included mice receiving bone marrow transplantation from HBV-immunized (anti-HBs positive) and non-immunized (anti-HBs negative) donors. RESULTS: At 9 weeks post bone marrow transplantation, tumor volume and serum alpha-fetoprotein levels in athymic mice receiving HBV-immune bone marrow cells were 11.5 mm3 and 363 ng/ml, respectively, as compared to 1579 mm3 and 19,000 ng/ml, in recipients of non-immune bone marrow transplantation (p<0.005). T-cell depletion of antiHBs+ immune bone marrow prior to transplantation decreased the anti-tumor effect but did not abolish it. A mild nonspecific, bone marrow-derived, graft versus tumor effect was observed in mice transplanted with human hepatoma cells that do not express HBsAg. CONCLUSIONS: Adoptive transfer of immunity to HBV facilitates suppression of experimental human HCC expressing HBsAg. This effect is the result of a combination of specific anti-viral surface antigen effect and a nonspecific graft versus tumor effect.
采用HBV免疫的供体进行BMT通过过继免疫而控制HBV感染性肝癌呢
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