OKT3治疗肝移植术后难治性排斥反应的护理

目前难治性排斥反应尚无明确的定义,通常把对大剂量激素冲击治疗疗效不好的排斥称为难治性排斥。OKT3是一种鼠源性抗CD3的单克隆抗体,它直接作用在淋巴细胞表面的抗原决定簇CD3复合物,注射OKT3后,血液循环中的淋巴细胞迅速下降[1]。其治疗耐激素难治性排斥反应逆转率为65%~95%[2]。台州医院肝胆外科自2001年8月至今共行原位肝移植手术28例,其中5例发生难治性排斥反应,经OKT3治疗后均被成功逆转,现将护理体会报道如下。1临床资料1·1一般资料本组5例,男4例,女1例;年龄42~56岁,平均48.5岁。原发病:肝硬化、小肝癌4例;胆汁性肝硬化1例。…     

Characterisation of blood and synovial fluid lymphocytes from patients with rheumatoid arthritis and other joint diseases by monoclonal antibodies (OKT series) and acid α-naphthyl esterase staining

Summary Mononuclear cell preparations from peripheral blood (PBL) and synovial fluid (SFL) of 27 Patients with rheumatoid diseases (15 patients with definite rheumatoid arthritis (RA), 10 with other inflammatory joint diseases (OJD), 1 with sarcoid arthritis (SA) and 1 with traumatic arthritis (TA) were examined for lymphocyte subpopulations determined by monoclonal antibodies of the OKT series and by the dot-like, acid -naphthyl esterase staining (ANAE) activity. In patients with classic, active RA, blood T cells carrying the OKT8⁺ (suppressor/killer) phenotype were significantly reduced leading to an elevated OKT4/OKT8 ratio of 4.1±0.4 compared with 2.1±0.1 in healthy controls.In 10 patients with OJD this diminution of OKT8⁺ cells in peripheral blood was less pronounced or absent. As regards SFL subpopulations, patients with RA and OJD exhibited a similar distribution pattern with an elevation of OKT8⁺, Ia⁺ and ANAE negative cells and a similar OKT4/OKT8 ratio of 1.5±0.3 and 1.6±0.4, respectively. Similar results were also obtained in the only patient with TA, whereas the patient with SA and one RA patient with relapse after surgical synovectomy exhibited high OKT4/OKT8 ratios, both in synovial fluid and peripheral blood. Neither the OKT markers nor the dot-like ANAE staining pattern were significantly correlated to parameters of systemic or local disease activity as estimated by erythrocyte sedimentation rate and a local disease activity index.     

Effects of in vivo CD8(+) T cell depletion on virus replication in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine

The role of CD8(+) T lymphocytes in controlling replication of live, attenuated simian immunodeficiency virus (SIV) was investigated as part of a vaccine study to examine the correlates of protection in the SIV/rhesus macaque model. Rhesus macaques immunized for >2 yr with nef-deleted SIV (SIVmac239Deltanef) and protected from challenge with pathogenic SIVmac251 were treated with anti-CD8 antibody (OKT8F) to deplete CD8(+) T cells in vivo. The effects of CD8 depletion on viral load were measured using a novel quantitative assay based on real-time polymerase chain reaction using molecular beacons. This assay allows simultaneous detection of both the vaccine strain and the challenge virus in the same sample, enabling direct quantification of changes in each viral population. Our results show that CD8(+) T cells were depleted within 1 h after administration of OKT8F, and were reduced by as much as 99% in the peripheral blood. CD8(+) T cell depletion was associated with a 1-2 log increase in SIVmac239Deltanef plasma viremia. Control of SIVmac239Deltanef replication was temporally associated with the recovery of CD8(+) T cells between days 8 and 10. The challenge virus, SIVmac251, was not detectable in either the plasma or lymph nodes after depletion of CD8(+) T cells. Overall, our results indicate that CD8(+) T cells play an important role in controlling replication of live, attenuated SIV in vivo.     

Generation of anti-tumour activity by OKT3-stimulation in multiple myeloma: in vitro inhibition of autologous haemopoiesis

Summary. T cells in multiple myeloma (MM) patients are highly susceptible to activation with the anti-CD3 monoclonal antibody (mAb) OKT3. When short-term OKT3 stimulation is carried out on bone marrow mononuclear cells (BMMC), large numbers of CD3⁺CD25⁺HLA-DR⁺ cells are rapidly generated and autologous malignant plasma cells are killed. OKT3 may thus be exploited in autologous bone marrow transplantation (ABMT) to purge residual plasma cells and simultaneously activate T cells to induce graftversus-leukaemia-like (GVL-like) activity upon reinfusion. However, the possible impact of ex-vivo short-term OKT3 stimulation on haematological recovery is unknown. The aim of this work was to investigate the effect of OKT3 stimulation in vitro on autologous haemopoietic progenitor cells (HPC) of MM patients. Colony formation by granulocyte-macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) was highly suppressed, although supernatants of OKT3-activated T cells contained up to 2500 pg/ml of granulocyte-macrophage colonystimulating factor (GM-CSF). T cell depletion completely prevented this suppression. Neutralizing antibodies against TNF-α, TNF-β and IFN-γ (which are also produced by OKT3-activated MM T cells) did not prevent it, and Transwell cultures showed that cell-to-cell contact was the main mechanism involved. OKT3-activated T cells also suppressed erythroid burst-forming units (BFU-E) and CFU-GM generation from HPC responsible for long-term maintenance of in vitro myelopoiesis. When tested on normal allogeneic BM, MM supernatants of OKT3-stimulated BMMC partially suppressed the generation of day 7 CFU-GM, but had no effect on day 14 CFU-GM. These data indicate that short-term stimulation of BMMC with OKT3 can be used to generate anti-tumour effector T cells for autologous adoptive immunotherapy. It is not a feasable approach for ex-vivo purging and activation procedures in ABMT because of its potent inhibition of autologous haemopoiesis.     

人腭扁桃体上皮中郎格罕氏细胞的观察

本文采用ATP酶组织化学法、OKT_6-免疫金银染色法和透视电镜(TEM)证明在人腭扁桃体上皮中有郎格罕氏细胞(LC)分布,主要位于上皮基底层和中间层,LC与上皮中淋巴细胞之间关系密切,认为LC在扁桃体的局部免疫反应中起重要作用.     

Preventive OKT3 treatment with cyclosporine (Sandimmun) for second kidney transplantation

Abstract A total of 793 kidney transplantations (KTx) were performed from November 1073 to March 1993. Two hundred and forty-two patients were treated with conventional immunosuppression (azathioprine + prednisolone) and all the others with cyclosporine (Sandimmun) and prednisolone (SIM + PRED). The survival of the second graft was less good in both therapeutic groups than that of the first ones, so we have started to use preventive immunotherapy with OKT3 (CILAG) in combination with SIM (both before operation) and PRED. We compared 32 SIM-PRED patients with 20 OKT3 + SIM + PRED patients. All underwent a second KTx. The two groups were found to be comparable and homogeneous with regard to 14 of 18 parameters analysed statistically. Statistically significant differences were found between the two groups as regards the frequency of acute rejection within 30 days (46.69% vs 20%), the delta creatinine value on the 1st and 2nd postoperative days (- 4,3: -8 vs -8.6: -19.7%), patient survival after 4 years (78.2 vs 100%), and graft survival after 1 and 4 years (-58.9: -42.8 vs -83.5: -83.5%), with better results in the OKT3 group. We conclude that the preventive use of OKT3 simultaneously with SIM + PRED for the second KTx is the method of choice to prevent rejection and improve survival. This treatment results in patient and graft survival following the second KTx being as good as after the first KTx with SIM + PRED.     

Anti-OKT3 response following prophylactic treatment in paediatric kidney transplant recipients

The anti-OKT3 response was studied in 40 paediatric kidney transplant recipients receiving OTK3 as a prophylactic treatment in association with azathioprine and prednisone. Only 1 patient experienced a reversible acute rejection episode while receiving OKT3. OKT3 induced a rapid disappearance of CD3+ cells, but significant proportions of CD3+ cells reappeared before the end of the treatment in 14 patients. Wide variations in circulating OKT3 levels were observed and in only 50% of patients could stable circulating OKT3 levels be detected until discontinuation of treatment. Anti-OKT3 antibodies detected by the enzyme-linked immunosorbent assay (ELISA) (anti-idiotypic and anti-isotypic antibodies) developed in 91% of patients. Anti-idiotypic antibodies detected by the immunofluorescence inhibition test were found in the sera of 71% of patients, always when high titres of anti-OKT3 antibodies were detected by ELISA. As it has recently been shown that anti-idiotypic antibodies are associated with failure of subsequent OKT3 treatment, we conclude that OKT3 should be restricted to steroid-resistant rejection crises in paediatric patients.     

Human T-cell subset requirements for the production of specific anti-influenza virus antibodyin vitro

Studies were undertaken to define the helper T-cell requirements forin vitro specific antibody production to influenza virus. Subpopulations of human T cells were separated on the basis of their reactivity with the monoclonal antibody OKT4. B cells cultured with OKT4⁺ T cells produced specific antibody to influenza virus, while B cells cultured with OKT4^– T cells did not. Irradiation (1200 rads) of the OKT4^– subset to potentially eliminate suppressor-cell activity did not augment the helper-cell function of that subset. Thus, unlike the cytotoxic T-cell response to influenza, help for anin vitro antibody response is mediated only by OKT4⁺ T cells.     

Review of immunosuppressive usage in pancreas transplantation

Throughout 1997, nearly 10 000 pancreas transplants have been performed worldwide, with 88% being simultaneous kidney transplants (SKPT). The current 1 yr patient survival rate exceeds 90% and pancreas graft survival (complete insulin independence) rate exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to registry data, rejection accounts for 32% of graft failures in the first year after pancreas transplantation. However, improvements are expected to continue with the evolution of treatment protocols. Most pancreas transplant centers employ quadruple drug immunosuppression with anti-lymphocyte induction with either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody induction therapy from 90% during the period 1987–1993 to 83% of pancreas transplants performed during 1994–1997. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite (AZA or MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune. In the last 2 yr, tacrolimus-based therapy has been used in approximately 20% of cases and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen after pancreas transplantation. At present, a number of centers are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF with or without antibody induction therapy. From 1994 to 1997, the 1 yr rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve in order to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycemic control with less immunosuppression and overall morbidity.     

特发性血小板减少性紫癜患者T淋巴细胞亚群的变化

用直接ＳＰＡ菌花环法体外测定１６例特发性血小板减少性紫癜（ＩＴＰ）患者外周血Ｔ细胞亚群，结果表明①患者平均ＯＫＴ８百分值明显高于正常（Ｐ＜０．０５），ＯＫＴ４±／ＯＫＴ８±比值明显减低（Ｐ＜０．０１），说明ＩＴＰ患者存在Ｔ细胞亚群紊乱。②患者外周血血小板计数与ＯＫＴ４±／ＯＫＴ８±比值呈显著正相关（ｒ＝０．７３９００），与ＯＫＴ８±百分值呈显著负相关（ｒ＝一０．６９４９４），故认为Ｔ细胞亚群测定适用于ＩＴＰ的病情监测、疗效及预后的判断。