Defective Human T-Cell Lymphotropic Virus Type I (HTLV-I) Provirus in 10 Chilean Seronegative Patients with Tropical Spastic Paraparesis or HTLV-I-Associated Myelopathy

We studied the presence of tax and ltr genes from human T-cell lymphotropic virus type I (HTLV-I) provirus in the peripheral blood mononuclear cells from 15 seronegative patients with tropical spastic paraparesis or HTLV-I-associated myelopathy by PCR. Only a region of the tax gene from 10 patients was amplified. The nucleotide homologies of six Chilean isolates to the ATK-1 clone ranged between 98.7 and 99.4%.     

Molecular Evidence for Transmission of Human T-Lymphotropic Virus Type II Infection by a Human Bite

Investigation of a human T-lymphotropic virus type II (HTLV-II) infection in a female Australian blood donor identified a human bite as the likely mode of transmission, confirmed by nucleotide sequencing of the proviral tax/rex from both donor and contact. We believe this to be the first report of the transmission of an HTLV by a human bite.     

Localization of Human Immunodeficiency Virus Antigens in Infected Cells by Scanning/Transmission-Immunogold Techniques

An application of high resolution scanning/transmission electron microscopy (STEM) and gold-labeling techniques for the rapid detection of human immunodeficiency virus (HIV) in infected cells has been developed. Experimental in vitro studies for detecting two HIV structural proteins, gp41 and p17, were performed following an indirect labeling procedure that uses monoclonal anti-p17 and anti-gp41 antibodies as primary antibodies and 40 nm gold-linked goat antimouse IgG as secondary antibodies. The cells were then studied by STEM in the scanning mode. Unambiguous localization of the viral antigens was possible by combining the three-dimensional image provided by the secondary electron image and the atomic number-dependent backscattered electron image for the identification of the gold marker. This technique combines both the morphological information and the rapid procedures of scanning electron microscopy with the precise and sensitive antigen detection provided by the use of STEM and immunological methods. The preliminary results of its application to the study of peripheral blood mononuclear cells from four anti-HIV-seropositive patients showing the presence of specific labeling in all of them suggest that it might prove useful for early detection of HIV infection before seroconversion, as well as for quantitative studies.     

Localization of Human Immunodeficiency Virus Antigens in Infected Cells by Scanning/Transmission-Immunogold Techniques

An application of high resolution scanning/transmission electron microscopy (STEM) and gold-labeling techniques for the rapid detection of human immunodeficiency virus (HIV) in infected cells has been developed. Experimental in vitro studies for detecting two HIV structural proteins, gp41 and p17, were performed following an indirect labeling procedure that uses monoclonal anti-p17 and anti-gp41 antibodies as primary antibodies and 40 nm gold-linked goat antimouse IgG as secondary antibodies. The cells were then studied by STEM in the scanning mode. Unambiguous localization of the viral antigens was possible by combining the three-dimensional image provided by the secondary electron image and the atomic number-dependent backscattered electron image for the identification of the gold marker. This technique combines both the morphological information and the rapid procedures of scanning electron microscopy with the precise and sensitive antigen detection provided by the use of STEM and immunological methods. The preliminary results of its application to the study of peripheral blood mononuclear cells from four anti-HIV-seropositive patients showing the presence of specific labeling in all of them suggest that it might prove useful for early detection of HIV infection before seroconversion, as well as for quantitative studies.     

Characterization of ERK Activation in Human Mast Cells Stimulated by Contact with T Cells

Close physical proximity between mast cells and T cells has been demonstrated in several human conditions. We have identified and characterized a novel mast cell activation pathway initiated by contact with T cells, and showed that this pathway is associated with cytokine release. It has been shown recently that Ras is activated in this pathway. Thus, in the present study we further explore the downstream events associated with Ras activation and cytokine release in human mast cells stimulated by contact with T cells. ERK activation in human mast cells stimulated by either contact with T cells or by crosslinking the FC epsilon receptor was studied. Photobleaching experiments were used to study ERK localization. Enzyme linked immunosorbent assay was used to study the cytokine release by human mast cells. We show that stimulation of human mast cells by contact with activated T cells results is sustained ERK activation. Furthermore, sustained ERK activation in these cells is associated with increased dwell time at the nucleus and with IL-8 release. Interestingly, when mast cells were stimulated by crosslinking the FC epsilon receptor I, ERK activation was transient. ERK activation was associated with a shorter dwell time at the nucleus and with TNF-α release. Thus, retaining ERK in the nucleus might be a mechanism utilized by human mast cells to generate different cytokines from a single signaling cascade.     

晚期肺癌患者调节性T细胞和IL-10表达的变化

探讨晚期肺癌患者的CD4＋CD25＋调节性T细胞（Treg）、IL-10及其他T细胞亚群表达的临床意义。检测晚期肺癌患者92例和正常对照者64名的IL-10（ELISA法）、CD4＋CD25＋调节性T细胞及其他T细胞亚群（流式细胞仪法）。结果显示：肺癌组血清IL-10明显大于对照组（278±34ng/L vs 122±65ng/L,P〈0.01）、CD4＋CD25＋Treg细胞明显大于对照组[（17.8±5.2）%vs（7.1±0.4）%,P〈0.01]、CD3＋、CD4＋、CD8＋CD28＋和NK细胞明显小于对照组[（58.4±7.8）%vs（78.2±6.4）%,P≤0.05;（34.4±7.6）%vs（44.9±8.4）%,P〈0.01;（9.4±3.6）%vs（16.5±2.7）%,P〈0.01;（9.4±3.6）%vs（18.5±7.2）%,P〈0.01]。CD8＋T细胞明显高于对照组[（37.8±6.5）%vs（31.8±5.1）%,P〈0.01]。CD4＋CD25＋Treg细胞、IL-10与CD8＋CD28＋细胞、NK细胞呈明显负相关。这些结果表明,CD4＋CD25＋Treg细胞与IL-10增多为晚期肺癌患者免疫功能受损的表现。     

同种异型T细胞抑制全身型MG患者AchR-Ab产生的研究

观察人T细胞对全身型重症肌无力 (MG )患者抗乙酰胆碱受体抗体 (AchR Ab )产生的影响。在体外用乙酰胆碱受体(AchR )为抗原诱导 30例全身型MG患者的淋巴细胞 ,并分别加入正常人T细胞和同种异体MG患者T细胞共同培养后 ,用酶联免疫吸附实验 (ELISA )检测MG患者淋巴细胞培养上清中AchR Ab的含量 ,并用微量细胞毒试验检测培养前后MG患者的T细胞亚群。结果显示 ,加入正常人T细胞组 ,其AchR Ab含量显著低于加入同种异体MG患者T细胞组和MG患者自身对照组 ,且正常人T细胞可使MG患者T细胞亚群间的比例发生改变 ,CD8+细胞数量明显增多 ,CD4+/CD8+比值明显降低。本文提示正常人T细胞能抑制全身型MG患者AchR Ab的产生 ,并对可能的机制及潜在的应用意义作了讨论。     

Activation of Human T and B Cells by Rabbit Anti-Human β2-Microglobulin

Rabbit anti-human β₂-microglobulin (anti-β₂m) increased the highest DNA synthesis in un-separated lymphocytes or artificially composed mixtures enriched in T and B cells. In enriched T and B cells no or low stimulation was seen. The maximal response by IgG anti-β₂m was seen in proportions of enriched T/B cells, being 3:1 for blood lymphocytes and 1:1 for spleen cells, which are the same as the physiological proportions of T and B cells in these lymphoid organs. Whereas unseparated lymphocytes gave a peat response on day 3, enriched B cells had a peak response on day 6. Fab anti-β₂m did not activate enriched T cells but increased DNA synthesis in enriched B cells to about the same extent as unseparated lymphocytes and mixtures of enriched T and B cells. The proportion of sheep erythrocyte rosette-forming cells (E-RFC) decreased after stimulation by anti-β₂m and increased after stimulation by phytohaemagglutinin. However, as revealed by autoradiography, a proportion of lymphocytes activated by anti-β₂m were E-RFC and this proportion increased with increasing stimulation by anti-β₂m. DNA synthesis induced by anti-β₂m was unchanged for spleen cells and slightly decreased for blood lymphocytes when phagocytic cells were removed by iron treatment. Supernatants from lymphocytes activated by anti-β₂m only induced low DNA synthesis in enriched T or B cells. Experiments with mitomycin treated cells indicate that cooperation and close contact between T and B cells are needed for activation by IgG anti-β₂m. T cells are needed for B cell activation by anti-β₂m and B cells are required for T cell activation to occur.     

High Prevalence of GB Virus C/Hepatitis G Virus RNA and Antibodies in Patients Infected with Human Immunodeficiency Virus Type 1

 The prevalence of GB virus C (GBV-C)/ hepatitis G virus (HGV) RNA and antibodies to the structural E2 protein was investigated in a cohort of HIV-1 infected patients. Of 346 individuals, RNA was detected in 143 and E2 antibodies were detected in 73, for an overall prevalence of 62.4%. Intravenous drug use and homosexuality were identified as major transmission risk factors. GBV-C/HGV RNA prevalence was associated with hepatitis B coinfection, whereas antibodies to E2 were associated with older age and lower CD4+ cell counts. GBV-C/HGV infection was frequent in this group of HIV-infected patients and was associated with older age, lower CD4+ cell counts, and the presence of hepatitis B surface antigen.     

Suppression of In Vitro Antibody Response by Spleen Cells of Mice Infected with Friend-Associated Lymphatic Leukemia Virus

The ability of spleen cells of mice infected with oncornaviruses to depress the in vitro antibody responsiveness of normal lymphoid cells was exploited in an attempt to clarify the role played by the lymphatic leukemia virus (LLV) component in the immunodepressive properties of the Friend leukemia complex. Spleen cells of mice infected with LLV or, for comparison, with the entire complex were added to cultures of sheep erythrocyte-primed uninfected spleen cells, and the antibody-forming cells produced by the latter, after antigen restimulation, were assayed. The addition within 2 days from culture initiation of low numbers of cells infected with either virus preparation suppressed all stages of the response affecting the production of both immunoglobulin M and immunoglobulin G antibody. The activity of infected cells resisted doses of ultraviolet radiation which inhibit cell multiplication but was abolished by disrupting the cells and was prevented by the presence of anti-LLV antibodies. The LLV-infected spleen cells responsible for suppression were not removed by treatments which selectively remove or kill macrophages and exhibited surface properties of B lymphocytes. These results were interpreted as indicating that the effect is due to virus (or viral products) released by B cells. The suppressing cells in the spleens of mice in the early days of Friend leukemia complex infection presented superimposable properties, supporting the concept that their activity is also due to the LLV they release in large quantities. However, in later stages of infection, the spleens of Friend leukemia complex-infected mice also contained non-B-suppressing cells possibly derived from the proliferation of nonlymphoid LLV-producing cells caused by the neoplastic process.     

Suppressor Cells Induced by Purified Protein Derivative of Tuberculin (PPD): the Suppression is Mediated by Cells that Proliferate in Response to Stimulation with PPD

Lymphocytes stimulated with purified protein derivative of tuberculin (PPD) were found to inhibit the PPD stimulation of fresh, autologous lymphocytes. This suppressor effect was exerted after preincubation with both high and low concentrations of PPD. Optimal suppression occurred after preincubation with PPD in concentrations of 5 micrograms/ml and higher, the same concentrations that gave optimal stimulation of DNA synthetsis in primary cultures. The suppressor effect was abolished completely by 'hot pulse' treatment and partly by treatment with colchicine during PPD preincubation, showing that the PPD-induced suppressr cells are generated by cell division. When fresh lymphocytes were incubated together with PPD-pretreated cells in cultures that were not stimulated with PPD, the PPD-stimulated lymphocytes exerted a stimulatory effect on the fresh lymphocytes. This effect was maximal for cells preincubated for 1 h with PPD, decreasing with increasing duration of preincubation with PPD. Possible explanations of this observation are discussed.     

T Cell Receptor Vα Gene Usage in Human T Cells Stimulated with SEE and SED

Vα gene usage in human T cells stimulated with SEE and SED was investigated by using polymerase chain reaction with specific primers. Vβ8 T cells from normal blood donors PBMC were sorted at day 5 after stimulation with SEE and analysed for TCR-Vα gene usage. Whole T cells stimulated with anti-CD3 MoAb or SED were also analysed and compared at different time points after stimulation. There was no biased Vα gene usage found as a response to either of the two superantigens. These results show that Vα gene usage of human T cells stimulated with SEE or SED is normal.     

Clinical Features of Seizures in Patients with Human Immunodeficiency Virus Infection

Patients with human immunodeficiency virus (HIV) infection have a higher burden of seizures, but few studies have examined seizures in HIV-infected individuals in Korea. A retrospective study was conducted to determine the epidemiology and clinical characteristics of seizures in patients with HIV infection. Among a total of 1,141 patients, 34 (3%) had seizures or epilepsy; 4 of these individuals had epilepsy before HIV infection, and the others showed new-onset seizures. Most patients exhibited moderate (200 to 500, n = 13) or low (below 200, n = 16) CD4 counts. The most common seizure etiology was progressive multifocal leukoencephalopathy (n = 14), followed by other HIV-associated central nervous system (CNS) complications (n = 6). Imaging studies revealed brain lesions in 21 patients. A total of 9 patients experienced only one seizure during the follow-up period, and 25 patients experienced multiple seizures or status epilepticus (n = 2). Multiple seizures were more common in patients with brain etiologies (P = 0.019) or epileptiform discharges on EEG (P = 0.032). Most seizures were controlled without anticonvulsants (n = 12) or with a single anticonvulsant (n = 12). Among patients with HIV infection, seizures are significantly more prevalent than in the general population. Most seizures, with the exception of status epilepticus, have a benign clinical course and few complications.

Graphical Abstract

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Circulating T Cells of Patients with Active Psoriasis Respond to Streptococcal M-Peptides Sharing Sequences with Human Epidermal Keratins

Psoriasis is a T-cell mediated inflammatory skin disease which has been associated with group A, β-haemolytic streptococcal infections. Four 20 a.a. long M6-peptides sharing 5–6 a.a. sequences with human epidermal keratins were identified. To investigate the role of potentially cross-reactive T cells in the pathogenesis of psoriasis, interferon-γ (IFN-γ) and interleukin-4 (IL-4) responses of circulating T cells to these peptides were analysed by ELISPOT and RT-PCR in 14 psoriatic patients, 12 healthy individuals and six patients with atopic dermatitis (AD). Untreated psoriatic patients' responses were significantly higher to these peptides than healthy and AD controls, while responses to a control M6-peptide, not sharing sequences with keratin, were negligible in all groups. No difference was found in response to streptokinase/streptodornase (SK/SD). M6-protein and peptides exclusively elicited IFN-γ production, with little IL-4 production, even in AD patients. Interferon-γ responses to all the M6-peptides were abolished after successful treatment of psoriatic patients, but responses to SK/SD were unaffected. The results indicate that active psoriasis is associated with Th1-like cells responding to streptococcal M6-peptides sharing sequences with human epidermal keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in susceptible individuals by M-protein specific Th1-like cells that cross-react with human epidermal keratin.