Hereditary abnormalities of the OKT4 human lymphocyte epitope in two families

The lymphocytes of two unrelated black individuals exhibited no immunofluorescent staining by a monoclonal antibody, OKT4, that reacts with T helper/inducer cells, but the lymphocytes reacted normally with four other monoclonal antibodies that identify T helper cells. Four first-degree relatives of these individuals were available for study. They had a normal proportion of OKT4⁺ lymphocytes but these cells had approximately half the normal number of OKT4 sites. This abnormality appears to be inherited as an autosomal recessive state.     

Distribution of Langerhans cells in clinically healthy human gingival epithelium with special emphasis on junctional epithelium

Abstract – Twenty-one biopsies of clinically healthy marginal gingiva from children, who performed conventional oral hygiene but received no additional professional prophylaxis, were studied in order to obtain information on distribution and density of Langerhans cells (LC) in the oral gingival epithelium (OGE), the sulcular epithelium (SE) and the junctional epithelium (JE). A simple freeze-separation technique was found to create acceptable histomorphology of JE in specimens obtained adherent to teeth, while partially and non-adherent ones were rejected. The majority of LC in OGE, were highly dendritic and stained intensively with OKT6 monoclonal antibodies. The distribution was network-like with a density of 21.0± 3.2 LC/0.1 mm² crosssectional epithelial area. A similar although less dense distribution was found in SE (8.6 ± 3.0 LG/0.1 mm²). These observations, confirm previous findings. In JE 2 groups of LC were identified: 1) Weakly stained LC with very few and short dendrites distributed in a scattered way (2.8± 1.4 LC/0.1 mm²) in the apical three-fourths of JE in most specimens. Present evidence suggests that these cells might be immature cells of Langerhans lineage. 2) Clusters of LC (9.4 ± 2.9 LC/0.1 mm²) with dendrites of moderate lengths and numbers and a varied fluorescence intensity; they were found in a few specimens in the coronal one-fourth of JE and at the border zone to SE. Such clusters might represent genuine variation in the distribution of LC or reactions to initial/ early plaque formation.     

Different Curcuminoids Inhibit T-Lymphocyte Proliferation Independently of Their Radical Scavenging Activities

PURPOSE: We investigated the inhibitory effects of curcumin, curcumin derivatives and degradation products on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation and the role of their radical scavenging activity. METHODS: OKT3-induced human PBMC proliferation was determined by measuring 3H-thymidine incorporation. Radical scavenging activity was evaluated by using an in vitro DPPH assay. RESULTS: OKT3-induced PBMC proliferation was inhibited by curcumin, isocurcumin, bisdesmethoxy-, diacetyl-, tetrahydro-, hexahydro-, and octahydrocurcumin as well as by vanillin, ferulic acid, and dihydroferulic acid with IC50-values of 2.8, 2.8, 6.4, 1.0, 25, 38, 82, 729, 457, and >1,000 microM, respectively. The investigated substances with the strongest effect on radical scavenging were tetrahydro-, hexahydro-, and octahydrocurcumin with IC50 values of 10.0, 11.7, and 12.3 microM, respectively. IC50-values of dihydroferulic acid, ferulic acid, and curcumin were 19.5, 37, and 40 microM. The substances with the lowest radical scavenging activities were vanillin, isocurcumin, diacetylcurcumin, and bisdesmethoxycurcumin with IC50 values higher than 100 microM each. CONCLUSIONS: Curcuminoid-induced inhibition of OKT3-induced PBMC proliferation depends on the number of carbon atoms and double bonds of the 1,6-heptadiene-3,5-dione structure as well as on the phenolic ring substitutes of the curcuminoids but is not correlated to their respective radical scavenging activity.     

OKT3治疗肾移植难治性排斥反应临床护理观察

目的:总结肾移植术后使用OKT3治疗难治性排斥反应出现的并发症的处理方法,探讨有效的护理措施。方法:回顾性分析2004年9月~2005年2月8例肾移植术后使用OKT3治疗难治性排斥反应患者的临床资料,总结出现的并发症和护理措施。结果:有效的治疗和护理措施使本组8例患者均有效控制了因OKT3使用出现的并发症。结论:相应的处理方法和护理措施可有效地阻止OKT3在的并发症的发展。     

OKT3-induced nephrotoxicity is associated with release of group II secretory phospholipase A2

Abstract. Administration of the murine IgG2a CD3 monoclonal antibody OKT3 exerts a transient nephro-toxic effect. Increased levels of group II secretory phospholipase A₂ (sPLA₂-II) might account for this nephrotoxicity as sPLA₂-II induces the biosynthesis of prostaglandins, vasoactive lipid mediators that influence glomerular haemodynamics and renal function. Furthermore, extracellular phospholipases seem to be involved in proximal tubular cell injury. We studied plasma sPLA₂-II levels in relation to circulating creatinine, tumour necrosis factor α, interleukin 6 and C-reactive protein levels in 15 renal allograft recipients receiving rejection treatment with OKT3. As a control group, we studied 15 renal allograft recipients receiving rejection treatment with methyl-prednisolone. A maximal fourfold increase in sPLA₂-II levels was observed 48 h after the first OKT3 administration, preceded by increased tumour necrosis factor α and interleukin 6 levels and accompanied by increased C-reactive protein levels. Creatinine levels reached a maximal increase 72 h after initiation of treatment. During methylprednisolone treatment no increase in any of the studied parameters was observed. Thus, administration of OKT3 induces increased sPLA₂-II levels, presumably via generation of cytokines. We hypothesize that sPLA₂-II may contribute to the nephrotoxic effect of OKT3 by inducing vasoconstrictive prostaglandins and renal tubular cell injury.     

Photopheresis in the treatment of refractory bronchiolitis obliterans complicating lung transplantation.

Photopheresis has been successfully used to treat heart allograft rejection and has had some initial success in the treatment of bronchiolitis obliterans (BO) following lung transplantation. This report describes five patients treated with photopheresis after the failure of augmented immunosuppression for BO. Four patients had a temporary stabilization of their airflow obstruction, and minimal side effects of the procedure were noted, although there were consequences from additional augmented immunosuppression (principally sepsis). Photopheresis may provide a safe modality for the treatment of BO that is unresponsive to standard and augmented immunosuppression.     

脾虚证患者部分细胞和局部免疫功能指标的测定

本实验对30例脾虚证和20名正常人的末梢血OKT系统T细胞亚群分类、淋巴细胞体外白细胞介素2(IL2)的分泌功能及局部免疫功能——唾液中分泌型免疫球蛋白A(SIgA)进行测定。结果:脾虚证患者与正常人相比,末梢血中T淋巴细胞总数(T_总)、辅助性T细胞(T_H)明显减少,抑制性T细胞(T_S)相对增多,T_H与T比值异常,单位淋巴细胞体外分泌IL2功能无明显改变;唾液SIgA水平在酸刺激前明显高于正常人,负荷实验储备力降低。说明脾虚证患者细胞免疫功能降低,免疫调节机制紊乱,免疫抑制占优势,消化道局部免疫功能低下。     

Humanized Antibodies: Enhancing Therapeutic Utility Through Antibody Engineering

The promise of antibody therapeutics has been greatly expanded by the development of monoclonal antibody technology and more recently antibody humanization. By transferring the mouse antibody binding site into a human antibody gene, we can engineer a “human antibody” which retains the specificity and biological effects of the original mouse antibody but has the potential to be nonimmunogenic in humans. Additionally, antibody effector functions can be improved through manipulation of the antibody constant region genes.

We have produced a humanized version of OKT3 with human IgG4 and kappa constant regions. This antibody retains all of the in vitro characteristics of murine OKT3 including induction of cytokine release and T cell activation markers. Humanized OKT3 has an affinity of 1.4 × 10⁹ M^?1 relative to a 1.2 × 10⁹ M^?1 affinity of murine OKT3. Substitution of a glutamic acid for leucine at residue 235 in the antibody constant region abrogates FcR I binding and causes a marked reduction of T cell activation. The humanized FcR mutant of OKT3 has potential to be an improved therapeutic for transplantation and may have applications in autoimmune disease treatment.     

Confirming a prediction of the calcium hypothesis of photoreceptor aging in mice

Prior work in healthy rats supported a calcium hypothesis of photoreceptor aging, wherein progressive age-related declines in photopic vision are explainable by the extent of earlier escalating d-cis-diltiazem–insensitive increases in photoreceptor L-type calcium channel (LTCC) activity in vivo. Unlike rats, healthy mice have relatively stable photopic vision until after 18 months of age. We therefore hypothesized that photoreceptor LTCC activity in mice would not progressively increase until after 18 months. In 2–5, 10, 18, and 26 months male C57Bl/6J mice, photoreceptor LTCC activity and retinal thickness were evaluated in vivo (manganese-enhanced magnetic resonance imaging) with some groups also treated with d-cis-diltiazem; visual performance was evaluated (optokinetic tracking). Data were calibrated for cone-only responses using mice without rod transducin (GNAT1−/−). Photopic vision was stable until after 18 months without retinal thinning or progressive increases in retinal manganese uptake. We measured an uptake spike at 10 months. This spike, unlike that in the rat, was diltiazem sensitive in the dark and diltiazem insensitive in the light. Between dark and light, uptake in inner retina of older mice was unequal (unlike that in 2–5 months mice); outer retinal uptake was similar to that in 2–5 months mice. Stable murine photopic visual performance and nonescalating photoreceptor LTCC activity before 18 months of age were consistent with a prediction of the calcium hypothesis. Stark differences in the temporal evolution of mouse and rat photoreceptor LTCC activity suggest the need for personalized identification of the retinal mechanisms contributing to declines in photopic vision to ensure success of future treatment efforts.