Preselection Thymocytes Are More Sensitive to T Cell Receptor Stimulation Than Mature T Cells

During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide–major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocyte maturation, such low affinity self-peptide–MHC ligands no longer provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide–MHC ligands. Remarkably, the preselection thymocytes were more responsive than mature T cells when stimulated with low affinity peptide variants, while both populations responded equally well to the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide–MHC complexes.     

Effect of iodine isotope on the pituitary-thyroid and immune systems of children living on the territories polluted by radionuclides

Examination of thyroid function and immune status of children living on the territories polluted by radionuclides in 1993–1994 revealed¹³¹I-dependent thyroid autoimmune reactions. These data indicate a possible effect of¹³¹I on the pituitary-thyroid and immune systems of children living on the radiation controlled territories. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 8, pp. 216–220, August, 1998     

Graves病患者血清可溶性白介素2受体的探讨

对２８例Ｇｒａｖｅｓ病的可溶性白介素２受体（ｓＩＬ２Ｒ）和各种甲状腺激素以及甲状腺自身抗体治疗前后比较，并进行逐步回归，结果表明：治疗后Ｇｒａｖｅｓ病患者除ＴＳＨ外，各种甲状腺激素及甲状腺自身抗体显著降低（Ｐ＜００１），并对ｓＩＬ２Ｒ的上升与下降呈显著相关。     

Delivery of Antigens to the MHC Class I Pathway Using Bacterial Toxins

Cytotoxic T lymphocytes (CTL) recognize antigens derived from endogenously expressed proteins presented on the cell surface in the context of major histocompatibility complex (MHC) class I molecules. Because CTL are effective in antiviral and antitumor responses, the delivery of antigens to the class I pathway has been the focus of numerous efforts. Generating CTL by immunization with exogenous proteins is often ineffective because these antigens typically enter the MHC class II pathway. This review focuses on the usefulness of bacterial toxins for delivering antigens to the MHC class I pathway. Several toxins naturally translocate into the cytosol, where they mediate their cytopathic effects, and the mechanisms by which this occurs has been elucidated. Molecular characterization of these toxins identified the functional domains and enabled the generation of modified proteins that were no longer toxic but retained the ability to translocate into the cytosol. Thus, these modified toxins could be examined for their ability to carry peptides or whole proteins into the cytosolic processing pathway. Of the toxins studied—diphtheria, pertussis, Pseudomonas, and anthrax—the anthrax toxin appears the most promising in its ability to deliver large protein antigens and its efficiency of translocation.     

Are hypodense eosinophils in children activated or immature?

In patients with allergic asthma and rhinitis high numbers of hypodense eosinophils (HE) have been demonstrated. In a previous study we reported that asthmatic and healthy children had more HE than their adult counterparts. We assumed that this might, in part, he due to the presence of immature eosinophils in children. To distinguish between immature and activated eosinophils, determination of eosinophil cationic protein (ECP) might be interesting as it is known that high serum levels of ECP are associated with increased activation of eosinophiis. In this study we determined (he levels of ECP in scrum in asthmatic and healthy children and adults trying to distinguish activated from immature eosinophils. We found that ECP levels were not increased in children (healthy and asthmatic) compared to adults (healthy and asthmatic). This supports the hypothesis that increased numbers of HE in childhood are, at least in part, immature eosinophils. Nevertheless, we could confirm that inflammation was present in children because soluble interleukin-2-receptor (slL-2R), a marker of lymphocyte activation, was higher in asthmatic children as compared to healthy children. IL-6, a marker of macrophage/monocyte activation, was not different in the different patient groups. We conclude that although signs of inflammation are present in childhood asthma, the increased numbers of HE in children are in part due to the presence of immature eosinophils.     

β-Adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats

Chronic/relapsing experimental allergic encephalomyelitis (CREAE) serves as an animal model for relapsing/remitting multiple sclerosis. Treatment with the β-adrenergic agonist isoproterenol or the β₂-adrenergic agonist terbutaline significantly suppressed both the first acute attack and the number of relapses in CREAE Lewis rats. The number of relapses was decreased even when treatment with β-adrenergic agonist was started after the onset of the first acute attack of CREAE. β-adrenergic receptor number was increased significantly on splenocytes from CREAE rats as compared to healthy controls or CFA-injected rats. Terbutaline treatment of CREAE rats lowered the splenocyte receptor number to normal values.     

荧光探针标记单克隆抗体在不同条件下的荧光变化

应用流式细胞术，探讨了不同贮存条件和时间对ＦＩＴＣ和ＰＥ标记单抗的荧光变化。结果表明４℃－３０℃１冷冻干燥对ＦＩＴＣ标主单抗无明显影响，ＰＥ偶联物皮４℃为宜。两种标记物检测的正常粉外周血Ｔ细胞及其亚群结果一致。     

进展期胃癌患者手术前后外周血T细胞及其亚群变化的研究

目的:研究进展期胃癌患者外周血T细胞免疫功能状态,手术对T细胞免疫功能的影响,以及对术后免疫治疗的指导。方法:采用间接免疫荧光染色流式细胞仪检测法,对43例进展期胃癌患者作手术前后外周血T细胞及亚群的测定,17例健康人作术前正常对照组。结果:与对照组相比,术前患者CD_3~+、CD_4~+细胞及CD_4~+/CD_8~+比值显著减少(P<0.01),而CD_8~+细胞无差异(P>0.05)。9例行非根治术者,手术前后T细胞及亚群无明显变化;而34例行根治术者,术后除CD_8~+细胞无变化外,CD_3~+、CD_4~+细胞及CD_4~+/CD_8~+比值均较术前有显著提高(P<0.01或P<0.05)。结论:术前进展期胃癌患者外周血T细胞免疫功能低下,行根治性切除术后得以改善。术后辅助免疫治疗或免疫化疗,以期提高生存率。     

Dopamine receptors on human T- and B-lymphocytes

The presence of functional dopamine receptors on differentiated cells of the mammalian immune system is still under discussion. This study has utilized (-)-[³H]sulpride as a ligand to detect the presence of recognition sites of the dopamine D₂ receptor family on human T- and B-lymphocytes. The (-)-[³H]sulpiride binding was of high affinity (K_d 0.9 nM ± 0.2 nM, specific, saturable (B_max 10.2 ± 1.4 fmol/10⁶ cells) and reversible. The pharmacological characterization of the recognition site suggests, similarities mainly with the D₂ and D₄ rather than D₃ subtype of dopamine receptor. Furthermore, dopamine treatment was able to reduce the intracellular cAMP levels of lymphocytes stimulated with forskolin, thus suggesting a potential functional significance of this dopamine receptor in mediating neural-immune interactions.