T-lymphocyte subpopulations in the peripheral blood and bone marrow of patients with aplastic anemia

Summary A decrease in the absolute number of total lymphocytes, OKT3⁺ and OKT4⁺ lymphocytes, and a normal number of OKT8⁺ lymphocytes were found in the peripheral blood of patients with aplastic anemia. The OKT4: OKT8 ratio was decreased in patients due to a reduction in the percentage of OKT4⁺ cells and 3 out of 18 patients had a ratio less than 1. The values of the OKT4:OKT8 ratio were not associated either with the severity of the disease or with treatment with androgens. There was no correlation between the OKT4:OKT8 ratio and the number of transfusions received by patients. On the other hand, studies performed with bone marrow lymphocytes showed that the OKT4:OKT8 ratio for both patients and controls was lower than that of the peripheral blood. Since the ratio of OKT4:OKT8 cells in aplastic and control bone marrow was similar no direct pathogenic role can be assigned to the marrow for the imbalance detected in the peripheral blood.     

Co-expression of T3 and surface immunoglobulin in neoplasms of 'early' B cells: a report of 2 cases

Chronic lymphocytic leukaemia (CLL) and well-differentiated lymphocytic lymphoma (WDLL) characteristically express surface membrane immunoglobulin (SIg) and react with monoclonal antibodies (Mabs) directed against a marker present on most normal T cells, namely T1. These SIg-positive B cells are usually negative for other T cell markers including T3 (CD3) which is expressed in all normal T cells. We report 2 cases, 1 CLL and 1 WDLL, in which the peripheral lymphocytes not only expressed monotypic SIg but also reacted with the T3-specific Mabs UCHT1 and OKT3 by indirect immunofluorescence or immunoperoxidase staining. False-positive staining by both UCHT1 and OKT3 was excluded by showing that lymphocytes sensitized with an irrelevant mouse Mab did not stain with second layer antibodies and that lymphocytes stained with second layer antibodies alone were always completely unreactive. Also, in 1 case the determinants demonstrated by both anti-Ig and UCHT1 were re-expressed after capping and shedding, i.e. appeared to be endogenous. The B cell origin of the CLL lymphocytes was supported by the finding of CK gene rearrangement in the absence of T beta gene rearrangement. It seems therefore that neoplasms of 'early' B cells may show bidirectional differentiation and co-express markers that are believed to be T-specific.     

Reduced dose OKT3 prophylaxis in sensitised kidney recipients

Prophylactic use of the monoclonal antibody OKT3 has been studied for the prevention of rejection in sensitised renal transplant recipients. Patients receiving a full dose (FD) regimen were compared to a subsequent consecutive group of patients receiving a reduced dose (RD) regimen. The characteristics of the two groups were not significantly different with regard to age, HLA mismatch and panel-reactive antibody (PRA) status. The number of days that OKT3 was given was 12.9±1.8 for the FD regimen and 11.3±2.8 for the RD regimen. The total dose of OKT3 given was 64.4±9 mg (FD) and 38.3±8.5 mg (RD). Patient survival at 12 months was 8/8 for FD and 17/17 for RD. Graft survival at 12 months was 7/8 for FD and 17/17 for RD. Creatinine at 24 months was 185±68 and 201±81 mol/l for FD and RD, respectively. A reduced dose regimen of OKT3 produced excellent and comparable results to the standard recommended fulldose regimen. The cost per patient was reduced 40% from £5676 for FD to £3344 for RD.     

OKT4／OKT8在Graves眼病中作用探讨

目的：探讨OKT4／OKT8在Graves眼病中的变化和意义。方法：67例初次确诊的Graves眼病病人，按有无突眼及甲亢分为不伴眼病的Graves病（29例）、合并眼病的Graves病（26例）和眼型Graves病（12例），以及正常对照组（19例），均采集空腹血样，经OKT抗体测定系统检测T淋巴细胞亚群。结果：四组间OKT4水平无差异（P＞0．05）；三实验组间OKT8变化无差异（P＞0．05），但均较对照组降低（P＜0．05）；OKT4／OKT8均较对照组升高9P＜0．05），且有眼病的Ⅱ、Ⅲ组远较无眼病的Graves病I组明显升高（P＜0．01）。结论：Graves眼病患者辅助性和抑制性T淋巴细胞亚群的不平衡较无眼病的Graves病患者更为严重。     

Simulect和OKT3诱导治疗应用于肾移植临床的疗效比较

目的评价Simulect和OKT3作为肾移植诱导治疗的有效性和安全性.方法将170例首次肾移植受者随机分为两组:Simulect组62,OKT3组108例.所有患者免疫抑制维持治疗均用环孢素A(CsA)/他克莫司(FK506) 霉酚酸酯(MMF) 泼尼松(Pred)三联.Simulect组:分别于术前2 h和术后4 d使用20mg Simulect:OKT3组:OKT3每天5 mg静滴,从术后第1天开始,连用7～10 d.观察两组在肾移植术后1年内急性排斥反应(AR)、移植肾功能延迟恢复(DGF)、毒副作用和人/肾存活情况.结果有34例发生AR,Sinulect组6例,OKT3组28例(P＜0.05),其中OKT3组5例出现2次或2次以上AR,7例AR需要ATG治疗逆转.移植肾功能延迟恢复(DGF)、细胞因子释放综合征、过敏反应等方面,Simulect组发生率明显低于OKT3组(6vs32,0vs49,0vs31,P＜0.01).Simulect组感染发生率低于OKT3组(16vs45;P＜0.05).OKT3组有2例移植肾切除,1例死于严重肺部感染.结论Simulect在肾移植免疫诱导治疗中疗效显著,副作用少,是一种强效安全的免疫抑制剂.     

CD3 Monoclonal Antibodies: A First Step Towards Operational Immune Tolerance in the Clinic

Type 1 diabetes (T1D) is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting β-cells within the pancreatic islets of Langerhans. It is caused by an immune-mediated inflammation, involving autoreactive CD4⁺ and CD8⁺ T lymphocytes that infiltrate the islets and initiate insulitis. The use of exogenous insulin is the current standard treatment. However, in spite of significant advances, this therapy is still associated with major constraints, including risk of hypoglycemia and severe degenerative complications. As T1D mainly affects children and young adults, any candidate immune therapy must be safe, and it must avoid a sustained depression of immune responses with all its attendant problems of recurrent infection and drug toxicity. In this context, inducing or restoring immune tolerance to target autoantigens would be the ideal approach. We refer to immune tolerance here as the selective damping of the damaging autoimmune response following a short treatment, while keeping intact the capacity of the host to respond normally to exogenous antigens. The therapeutic approach we discuss in this article originates from attempts to induce tolerance both to soluble antigens and tissue antigens (i.e. alloantigens and autoantigens) by using biological agents that selectively interfere with lymphocyte activation, namely polyclonal and monoclonal anti-T cell antibodies. The challenged dogma was that, in an adult-primed immune system, it was not possible to restore self-tolerance therapeutically without the use of exogenous autoantigen administration. The reality has been that, in diabetes, endogenous host autoantigen can fulfill this role because a significant amount of functioning β-cells remains, even at the time of established hyperglycemia. Experimental results obtained in the 1990s showed that a short-term CD3 antibody treatment in recently diagnosed diabetic non-obese diabetic (NOD) mice induced permanent remission of the disease by restoring self-tolerance. Based on these findings, phase I, II, and III trials were conducted using two distinct humanized Fc-mutated antibodies to human CD3, namely ChAglyCD3 (otelixizumab) and OKT3γ1 Ala-Ala (teplizumab). Overall, when dosing was adequate, the results demonstrated that CD3 antibodies preserved β-cell function very efficiently, maintaining significantly high levels of endogenous insulin secretion in treated patients for up to 24 months after treatment. These data provided the first proof of concept for a long-term therapeutic effect in T1D following a short course administration of a therapeutic agent. Our aim is to review these data and to discuss them in the context of the pitfalls linked to pharmaceutical development, especially in the context of pediatric patients, as in autoimmune diabetes.     

骨质疏松症知识问卷的信度和效度测定

目的分析翻译和修订的骨质疏松症知识问卷的信度和效度.方法根据中国文化背景对骨质疏松症知识问卷进行翻译和修订,并测试291例社区中老年人.随机抽取其中66例进行重测.结果内部一致性信度α系数0.83～0.87.重测Pearson相关系数0.75～0.82（P＜0.001）,配对t检验,P＜0.05.条目分析除第3条外,均具有较好的区分度,高低分组之间差异有显著性（P＜0.001）.结论骨质疏松症知识问卷的信度与效度良好,项目设置适用于骨质疏松症知识的评价.     

Unusual Lack of the Epitope Recognized by OKT4 on the Helper/Inducer T Lymphocytes

Lack of the epitope recognized by OKT4 monoclonal antibody on the helper/inducer T lymphocytes in a 14-year-old boy with IgA nephritis is described. The lymphocytes reacted normally with OKT3 /Leu4 and OKT8/αLeu2a monoclonal antibodies but not with OKT4 monoclonal antibody. Studies with other monoclonal antibodies (αLeu3a, OKT4A, OKT4B, OKT4C, OKT4D) which also identify the helper/inducer T lymphocyte subset revealed that cells of this population were present in normal numbers among the lymphocytes of the peripheral blood. Staining with OKT4 plus αLeu3a in normal persons indicated that T4 antigen is present on a small population of lymphocytes which lack Leu3a antigen. Further, the intensity of staining of the majority of cells in the subpopulation is increased when these two fluorescienated antibodies are used together. In this patient neither this small OKT4⁺ Leu 3a^- population nor the cells bearing the Leu3a antigen showed OKT4 staining. The findings in the surface marker analysis of E+ OKT8- peripheral lymphocytes which were achieved by panning of the patient's peripheral cells indicated the existence of a population of E⁺OKT8^- peripheral lymphocytes which were achieved by panning of the patient's periphera cells indicated the existence of a population of E⁺ (4A⁺4B⁺4C4D⁺)αLeu3al⁺ ly mphocytes in this patient. Lymphocyte responses to PHA, ConA and PWM, however, were all within normal range. Further, this patient had normal serum immunoglobulin levels and exhibited no symptoms or signs of immunodeficiency. These findings indicate that the patient under study has functionally normal helper/inducer T lymphocytes which lack the epitope recognized by OKT4 monoclonal antibody.     

Developmental Maturations of B Cell Differentiation Ability and T Cell Regulatory Function in Man1

As assessed in Nocardia mitogen system, B cell differentiation ability and T cell help for IgM-production appeared to be nearly maturated at birth, but those for IgG- and IgA-production were still deficient in cord blood and required much more time for their maturation. Deficit in concanavalin A-inducible humoral suppressor activity and marked excess in pokeweed mitogen-inducible one were peculiar properties of T cells in the early developmental period of life. The T cell subset in cord blood defined by OKT4 monoclonal antisera was much more suppressive on B cell differentiation than did another OKT8⁺ subset, suggesting functional aberration of cord T cell subsets from corresponding adult ones.     

Cytomegalovirus retinitis in a young homosexual male with acquired immunodeficiency

A case is reported of histopathologically documented CMV retinitis. It is part of a recently appreciated syndrome in young homosexual men, in which cellular immune deficiency has been documented and in which CMV infection may play a role. This case demonstrates that CMV retinitis is not excluded by negative CMV serology or cultures.