Distribution of acid alpha-naphthyl acetate esterase among human T lymphocyte subsets

Human T lymphocyte subsets, identified by means of OKT3, 4 and 8 monoclonal antibodies, were isolated by a fluorescence activated cell sorter (FACS IV) and analyzed for distribution of alpha-naphthyl acetate esterase (ANAE) activity. As compared to OKT8⁺ lymphocytes a higher proportion of OKT4⁺ lymphocytes was ANAE-positive exibiting a spot or dot-like pattern in the cytoplasm. OKT8 and 4 positive subsets showed a similar ANAE distribution in diffuse granular form. Although OKT4 and OKT8 populations presented a different ANAE dot-like reactivity, this marker did not allow as clear a distinction between them as that reported for T_G and T_M lymphocytes.     

Cytomegalovirus infection and disease after liver transplantation

Cytomegalovirus is the single most important pathogen in clinical transplantation. Although much progress has been made in our understanding of the molecular biology and epidemiology of CMV infection and in our ability to diagnosis and treat CMV disease, it remains a major cause of morbidity but is no longer a major cause of mortality after liver transplantation. Risk factors for CMV disease after liver transplantation include donor and recipient serologic status, the use of antilymphocyte therapy, and retransplantation. CMV disease occurs early after transplantation, and the most frequent site of disease is the hepatic allograft. We have treated 79 patients with intravenous ganciclovir, with ultimate control of disease achieved in 69 patients (87.3%). Preliminary results using intravenous immunoglobulin and oral acyclovir for CMV prophylaxis in high-risk patients have been encouraging. In addition to producing clinical syndromes, CMV may have direct immunologic effects and is a marker of the net state of immunosuppression.     

Disease activity markers in multiple sclerosis. Another look at suppressor cells defined by monoclonal antibodies OKT4, OKT5, and OKT8

Here we report our experience in profiling peripheral blood T-cell subsets with the monoclonal antibodies OKT4, OKT5 , and OKT8. Lymphocyte surface phenotype was measured by automated cytofluorometry. In a population survey, we were unable to detect differences between patients with multiple sclerosis (MS) and control subjects when we compared ratios of lymphocytes of helper cell phenotype (OKT4) to those with suppressor cell phenotype ( OKT5 and OKT8). No differences could be established between patients with stable disease, chronic progressive disease, or those with active disease. In a study of 10 patients followed through an exacerbation, we were also unable to define perturbations in these lymphocyte ratios that correlated with disease activity. Detailed analysis of the fluorescence histogram, which examines the entire spectrum of cell surface fluorescence intensity in a population of lymphocytes, was also not useful in predicting disease activity in these patients. The discrepancies between these data and other reports in the literature are discussed. We propose that these reagents are inadequate indices of disease activity, and that until other monoclonal reagents are developed and studied, the suppressor cell compartment is best assessed by assays of function.     

The role of OKT3 in clinical transplantation

OKT3 is a murine monoclonal anti-T cell antibody that is directed to CD3, a five-chain molecular complex found in association with the T cell receptor for antigen. OKT3 was the first monoclonal antibody to be used in organ transplantation and during the past 10 years there has been extensive experience of its use both for preventing and treating rejection in organ transplantation. OKT3 blocks T cell function by modulating CD3 and the T cell receptor from the T cell surface. A reaction to OKT3 results from cytokines released when OKT# first reacts with T cells. This reaction is generally mild but can be severe. First rejections following kidney transplantation are reversed in approximately 95% of cases. Steroid-resistant rejections are also susceptible to OKT3 but in only approximately 75% of cases. When used for prophylaxis, OKT3 completely blocks rejection in 95% of patients and significantly delays the onset of rejection in those who do reject. Antibodies to OKT3 are produced in approximately 75% of patients receiving it. However, seldom are the antibodies to OKT3 present in high titer and only in those cases is successful re-use of OKT3 prevented. As is the case with all potent immunosuppressive drugs, the use of OKT3 is associated with increased viral, specifically cytomegalovirus, infections. However, it appears that reduction of concomitant immunosuppression decreases the incidence of severe infections. Unquestionably, OKT3 has been a useful addition to the immunosuppression used for organ transplantation. In addition, its use has stimulated research on other monoclonal antibodies for use in organ transplantation.     

Restoration of decreased suppressor cells by vitamin B12 therapy in a patient with pernicious anemia

A unique case of pernicious anemia is described. Initially, the percentage of OKT8-positive blood cells was markedly decreased, resulting in an increase in the OKT4/OKT8 ratio. The level of OKT8-positive blood cells was, however, returned to normal after vitamin B12 therapy. The finding may propose a possible role of the imbalance of blood lymphocyte subpopulations on the pathogenesis of pernicious anemia and also a responsibility of vitamin B12 for such a selective reduction in the OKT8-positive blood cells.     

用la和OKT单克隆抗体研究胃癌和食管癌患者的免疫功能

用Ia和OKT单克隆抗体对经纤维胃镜确诊的食管癌17例、胃癌20例及正常人17名的外周血淋巴细胞进行分类。空腹抽血5ml,提取淋巴细胞,用Ia、OKT_3、OKT_4、OKT_8抗体和兔抗鼠IgG荧光抗体作免疫荧光染色。计数100个淋巴细胞中阳性细胞的百分比。结果:正常人T淋巴细胞(OKT_3阳性)为74.03±2.19,辅助性T淋巴细胞(OKT_4阳性)为49.02±3.88,抑制性T淋巴细胞(OKT_8阳性)为28.98±3.89,B淋巴细胞(Ia阳性)为20.86±2.98,OKT_4/OKT_8比值为1.72。食管癌患者与胃癌患者的OKT_4为41.27±5.98与39.33±7.29,明显低于正常人组;OKT_8为40.09±6.11与36.26±7.21,较正常人组显著增加;OKT_4/OKT_8比值为1.10与1.15,显著小于正常人组。说明进展期肿瘤患者的免疫功能均处于失调状态。     

In vitro B-lymphocyte switch disturbance from IgM into IgG in IgM mesangial nephropathy

In vitro immunoglobulin (Ig) synthesis using a co-culture technique after activation of lymphocytes with pokeweed mitogen, T-cell subsets and interleukin-2 (IL-2) production was studied in 10 children who suffered from IgM mesangial nephropathy (IgMN), 10 children who suffered from minimal change nephrotic syndrome (MCNS) with hypercellularity and 6 children who suffered from MCNS with normal cellularity during the acute nephrotic phase. Reduced in vitro IgG production was found in the presence of OKT8 cells from all groups of patients. However, in vitro IgM production was increased only in OKT8 cells from IgMN and MCNS patients with hypercellularity. In vitro Tac expression on the OKT8 cells, IL-2 production, T-cell subsets including Leu2a⁺15⁺ (suppressor T-cells), Leu2a⁺DR⁺ (activated suppressor T-cells) and Leu3a⁺8⁺ (suppressor T-cell inducer) were all increased in IgMN and MCNS patients with hypercellularity. There was a significant correlation between in vitro IgM production by co-culture technique and IL-2 production. These results strongly suggest the hyperfunction of isotype-specific suppressor T-cells which may affect the switch of IgM B-cells to IgG B-cells in IgMN and MCNS patients with hypercellularity and may be used to explain in part the clinical findings of lower serum IgG and increased IgM in those patients.     

OKT3治疗肾移植术后急性排斥反应的观察及护理

目的探讨OKT3治疗肾移植术后急性排斥反应的护理方法。方法对4例慢性肾功能衰竭行同种异体肾移植术后发生急性排斥反应的患者应用OKT3进行治疗,治疗前给予心理护理,减轻患者的焦虑,使其很好地配合治疗;治疗期间重点做好不良反应的护理,预防及减轻不良反应的发生。结果治疗过程中未出现感染、肺水肿等不良反应。结论精心的护理可预防和减轻OKT3的不良反应的发生,提高治疗效果。     

Antithymocyte globulin use for treatment of biopsy confirmed acute rejection is associated with prolonged renal allograft survival

Antithymocyte globuline (ATG) and OKT3 have been used for treatment of severe biopsy confirmed acute renal allograft rejection (BCAR). We report results on graft and patient survival including 399 subjects diagnosed with BCAR treated with either ATG or OKT3. Multivariable analyses including Banff scores were performed following three different strategies to account for confounding variables. Fifty per cent of subjects in the OKT3 group had a functioning graft 6.3 years after diagnosis of BCAR, but 74% of ATG patients' grafts were still functioning at that time point (log rank P  = 0.006). Median actual graft survival was only 4.6 years in the OKT3 subjects, but 9.5 years for ATG-treated patients (log rank P  = 0.004). Multivariable analysis revealed that the risk for functional graft loss was significantly elevated in the OKT3 compared to ATG patients (HR = 1.79, 95% CI 1.06–3.02, P  = 0.029). The risk for actual graft loss, counting death as event, was also significantly elevated in the OKT3 patients (HR = 1.73, 95% CI 1.09–2.74, P  = 0.019). The hazard of death was not different between the groups (HR = 1.55, 95% CI 0.87–2.77, P  = 0.137). These data suggest that rejecting renal allografts treated with ATG exhibit longer graft survival than OKT3 treated transplant kidneys. Causal inference, however, cannot be drawn from this associational study.     

High or low dose steroid therapy for acute renal transplant rejection after prophylactic OKT3 treatment: a prospective randomized study

In this prospective randomized study, acute renal transplant rejections occurring in patients who received prophylactic OKT3 therapy were treated with either 3 pulses of 8 mg/kg methylprednisolone (MPS) in an alternate-day regimen (total dose 25 mg/kg in 1 week, H group, n = 24) or 5 daily pulses of 3 mg/kg MPS (total dose 17 mg/kg, L group, n = 22). Acute rejection was proven by biopsy in more than 85% of cases in both groups. No difference was observed in rejection reversal (H 88%, L 91%), graft losses in the following 3 months (H 11%, L 4%) or the time evolution of the serum creatinine levels. The number (H 14, L 21) as well as the nature and severity of infections were similar in both groups. Only one death occurred in a patient who received OKT3 rescue therapy for corticoresistant rejections and developed Epstein-Barr virus (EBV)-related lymphoma. In conclusion, low dose MPS pulses appear as effective and safe as a higher dose to reverse acute rejection occurring after OKT3 prophylaxis. Thus, we favour the use of the low dose regimen in these patients.