Effects of Carbamazepine on Murine Humoral and Cellular Immune Responses

Summary: Oral administration of carbamazepine (CBZ)(15, 10, or 5 mg/kg) to mice significantly decreased both humoral and cellular immune responses evaluated by enumeration of direct and indirect plaque-forming spleen cells (PFC) and delayed–type hypersensitivity reaction (DTH) against sheep red blood cells (SRBC) as compared with those observed in normal control animals. Moreover, spleen T cells obtained from CBZ–treated donor mice were capable of decreasing both PFC and DTH responses of normal spleen cells transferred into lethally irradiated recipient animals. The immunodepressor effect of CBZ was observed even though administration of CBZ induced augmentation of spleen cellularity.     

Response of V beta 8.1+ T cell clones to self Mls-1a: implications for the origin of autoreactive T cells.

Clonal deletion and anergy are two major mechanisms of self-tolerance. However, the molecular mechanisms underlying clonal deletion and anergy, as well as the threshold of TCR affinity/avidity required for these processes, are not known. Expression of the V beta 8.1 TCR correlates with the reactivity of the T cells to the minor lymphocyte stimulating locus-1a (Mls-1a) and T cells expressing this TCR are deleted in the thymus of Mls-1a mice. Similarly, in TCR V beta 8.1 transgenic mice, the number of CD4+CD8-T cells is reduced in Mls-1a mice. However, small numbers of CD4+CD8-T cells remain in the periphery of adult Mls-1a transgenic mice. We have generated T cell clones from TCR V beta 8.1 transgenic mice by stimulation of lymph node T cells with C57BL/6 alloantigens. Interestingly, CD4+CD8-V beta 8.1+ clones isolated from the transgenic mice of Mls-1a background responded to the self-antigen Mls-1a, to which they did not respond in primary assay. Reactive patterns of the clones were compared with clones derived from Mls-1b mice. Proliferation and cytokine production of the clones from Mls-1a mice to the self-antigen Mls-1a were generally reduced when compared with clones from Mls-1b mice. More importantly, T cell clones from Mls-1a mice required more Mls-1a antigen for their activation, and were more susceptible to the inhibitory effects of anti-CD4 antibody on the proliferative responses to Mls-1a than those from Mls-1b mice. These results suggest that the T cell receptor on clones derived from Mls-1a mice have functional but reduced affinity/avidity for self-antigen Mls-1a.     

Inhibition of IL-2 synthesis by donor-pecific suppressor T cells in a renal transplant recipient

Abstract A study was conducted to elucidate the mechanism of donor-pecific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-pecific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-pecific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-pecific suppressor T cells that produced a humoral non-pecific suppressive factor only when stimulated by the donor PBL, and this factor suppressed PLR and CML by inhibiting IL-2 synthesis of the PBL.     

维生素E对小鼠胸腺和脾脏T淋巴细胞转化及MΦ诱导IL－1的影响

ＶＥ缺乏组、１／３需要量组、需要量组、３倍需要量组、２０倍需要量组的初断奶小鼠喂养８周后观察Ｔ淋巴细胞转化及Ｍ中诱导ＩＬ－１反应。结果表明，ＶＥ增强半合适、合适剂量ＣｏｎＡ诱导的胸腺、脾脏Ｔ淋巴细胞转化，且半合适剂量诱导的反应高于合适剂量，ＶＥ增强合适剂量ＰＨＡ诱导的脾Ｔ细胞反应，但不影响其诱导胸腺Ｔ细胞反应。ＶＥ还提高ＭΦ诱导ＩＬ－１生成。上述实验以缺乏组反应最弱，３倍量组反应最强，而２０倍量组反有下降趋势。     

Methotrexate therapy of oral corticosteroid-dependent asthmatics reduces serum immunoglobulins: correlation with clinical response to therapy

BACKGROUND: Concomitant methotrexate (MTX) therapy of oral corticosteroid (CS)-dependent asthmatics has been shown to spare CS therapy, but the mechanism is unknown. In a previous report, we showed that MTX increases T cell inhibition by CS. In this report we focus on effects of MTX on immunoglobulin concentrations and their possible clinical relevance. OBJECTIVE: To monitor changes in circulating leucocytes and Ig in a group of these patients during MTX therapy, and to relate these changes to clinical 'response' as defined by oral CS reduction. METHODS: Sixteen severe asthmatics dependent on oral prednisolone 15 (7.5-25) mg/day in addition to high dose inhaled CS were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. Prednisolone dosages were maintained constant for 12 weeks then reduced systematically over the next 16 weeks provided that asthma control did not deteriorate. Patients were classified a priori as 'responders' or 'non-responders' to MTX (reduction of initial oral prednisolone requirement by >or=50% or <50%, respectively). Patients were followed-up for a further 12 weeks after MTX withdrawal. Serum Ig and differential blood leucocyte counts were measured at baseline, 12, 28 and 40 weeks. RESULTS: MTX therapy allowed significant, but individually variable, reductions in oral prednisolone dosages (P<0.00001) without alteration of lung function or symptoms. This was associated with significant reductions in mean serum concentrations of Ig of all classes, which reversed following MTX withdrawal. Reductions in IgE and IgG were significantly greater in the MTX 'responders' as compared with 'non-responders', and changes in IgE, IgG and IgM correlated with changes in prednisolone requirements. Differential blood leucocyte counts showed no significant variation. CONCLUSION: MTX therapy reduced oral CS requirements in these severe asthmatics to a degree which correlated with reduced circulating Ig but not lymphopaenia, suggesting a possible cause and effect relationship. These reductions might also contribute to the documented incidence of opportunistic infection in these circumstances.     

Basic principles of immunology (immune response) for hemapheresis practitioners

Advances in medical knowledge and technology have identified the essential elements involved in the human immune system, their relationships and interactions, and offer more advanced concepts in the design, function, and maintenance of immune response. Immune response begins with the earliest progenitor cell and transfers its legacy of protection through white blood cells and the complement system. A basic understanding of immunology is essential to the hemapheresis practitioner as new treatment regimens requiring hemapheresis interventions develop. © 1992 Wiley-Liss, Inc.     

大肠癌组织中免疫抑制因子和病理分期关系的探讨

本文观察16例大肠癌病人的癌组织培养上清液对人T细胞的增殖,ZL—2产生的影响和病理Dukes分期的关系,发现癌组织的TDSF对T细胞的增殖有显著抑制作用,对ZL—2的产生抑制作用不明显,对T细胞增殖率在DukesA与B期,其值与对照有显著差异(0.01P<0.05).在C期有非常显著差异(P<0.01).说明大肠癌组织确实分泌有能造成宿主免疫功能下降的抑制物质.且免疫作用不是通过ZL—2环节发生.     

应用单克隆抗体检测肺癌病人外周血中T细胞亚群

本文应用单克隆抗体检测33例原发性肺癌病人治疗前后外周血中T淋巴细胞亚群变化。结果提示:肺癌病人外周血中T细胞亚群明显有别于正常人,主要表现为T_H细胞降低和T_S细胞升高以及T_H/T_S比值明显倒置。短期观察结果表明,肺癌病人外周血中T_S细胞持续升高和T_H/T_S比值持续降低者,预后不良。临床检测T细胞亚群变化及它们的动态变化可作为判断宿主抗肿瘤免疫功能状态、病情发展和预后的敏感指标。     

抗乙肝胎盘转移因子的特异免疫活性观察

本研究由ＨＢＶＭ－Ａｂ阳性胎盘提取的抗乙肝胎盘转移因子（ＰＳＴＦ）的特异免疫活性证明，经注射，小鼠外周血淋巴细胞明显增多，胸腺重量和指数亦显著增加，酯酶染色证明７５％属Ｔ－样淋巴细胞，２５％属Ｔｈｙ－样淋巴细胞，人白细胞或小鼠白细胞体外转移ＰＳＴＦ特异免疫活性、或豚鼠和小鼠体内转移ＰＳＴＦ特异免疫活性，再取其白细胞作白细胞粘附抑制、白细胞移动抑制、特异淋巴细胞转化、小鼠足掌注射和诱生γ－干扰素试验