DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells

Human contact with fungi does not usually lead to pathological consequences, as the immune system manages to defeat the invader pathogens. Nevertheless, under immune suppression, fungi overcome immune defenses and cause diseases that range from nonserious colonizations of keratinizated tissue (Dermatophytosis) to life threatening disseminated infections (Aspergillosis). Host defenses against fungi rely on innate and adaptative responses, with dendritic cell (DC) and macrophage surface receptors having a major role in the recognition of fungal pathogens and in the orchestration of an effective immune response. DC-SIGN is a C-type lectin involved in the recognition of bacterial, viral and parasitic pathogens, as well as in interactions between cells of the immune system. Its expression is restricted to DCs and subsets of macrophages. Here we show that DC-SIGN mediates the binding and capture of Aspergillus fumigatus and keratinophylic fungi, including Chrysosporium tropicum, by human DCs, describe the requirements of these interactions and discuss their potential involvement in the onset and persistence of pulmonary fungal infections.     

Impaired T cell proliferation, increased soluble death-inducing receptors and activation-induced T cell death in patients undergoing haemodialysis

Haemodialysis is a widespread option for end-stage renal disease (ESRD). Long-term success of dialysis is, however, limited by a high rate of serious bacterial and viral infections. We compared T cell functions in ESRD patients undergoing haemodialysis (n = 20), or were not dialysed and received conventional medical treatment (n = 20). Healthy volunteers (n = 15) served as controls. The T cell phenotype was examined by immunofluorescence using fluorochrome-labelled monoclonal antibodies and FACS analysis. The concentration of soluble CD95/Fas and of tumour necrosis factor-alpha receptor type 1 (sTNFR1) in the sera was quantified by ELISA. Activation-induced programmed T cell death was triggered by anti-CD3/CD28 antibodies and measured by 7-AAD staining. All immunological tests were performed at least 1 month after dialysis initiation. T cell proliferation in response to phytohaemagglutinin or anti-CD3 monoclonal antibodies was moderately diminished in non-dialysed patients and markedly reduced in haemodialysis patients compared to healthy controls (P < 0.01 and P < 0.001, respectively). In a mixed lymphocyte culture the proliferative response of T cells from dialysed patients was significantly diminished (P < 0.001). T cells of both non-dialysed and dialysed patients have augmented CD95/Fas and CD45RO expression, increased sCD95/Fas and sTNFR1 release and spontaneously undergo apoptosis. Culture of T cells from haemodialysis patients with anti-CD3/CD28 antibodies increased the proportion of CD4(+) T cells committing activation-induced cell death by a mean 7.5-fold compared to T-helper cells from non-dialysed patients (P < 0.001). Renal failure and initiation of haemodialysis results in a reduced proliferative T cell response, an aberrant state of T cell activation and heightened susceptibility of CD4(+) T cells to activation-induced cell death.     

氧化苦参碱对LAK细胞活性的影响

ＬＡＫ细胞具有很强的广谱杀瘤作用，而氧化苦参碱具有较强的免疫抑制作用。本文研究了氧化苦参碱对ＬＡＫ细胞活力的影响，结果表明：氧化苦参碱可抑制ＩＬ－２对小鼠脾细胞的促增殖作用，并且对ＩＬ－２活化ＬＡＫ细胞杀伤Ｐ８１５的能力也有抑制作用。当ＩＬ－２（５００ｕ／ｍｌ）与２００μｇ／ｍｌ的氧化苦参碱共同孵育４ｄ后，可使ＬＡＫ细胞杀瘤能力（在效靶比为１００：１时）的８２．５％被抑制。同时氧化苦参碱本身对Ｐ８     

Renal Na+, K+-ATPase in Dahl salt-sensitive rats: K+ dependence,effect of cell environment and protein kinases

Na⁺, K⁺-ATPase in renal epithelial cells plays an important role in the regulation of Na⁺ balance, extracellular volume and blood pressure. The function of renal Na⁺, K⁺-ATPase in Dahl salt-sensitive (DS) rats, an animal model for salt-sensitive hypertension, and Dahl salt-resistant (DR) rats has been studied. In Na⁺, K⁺-ATPase partially purified from renal cortex, affinities and the Hill coefficients for Na⁺ and K⁺ activation were similar in DS and DR rats. Only one component of low ouabain affinity site was found in both strains, indicating the presence of the al isoform. Protein kinase C and cAMP-dependent protein kinase phosphorylated Na⁺, K⁺-ATPase α subunit in DS and DR rats, and the phosphorylation by protein kinase C was associated with an inhibition of enzyme activity. The kinetic parameters for K⁺ activation were also studied in a preparation of basolateral membranes and were found to be similar in DS and DR rats. In a preparation of cortical tubule cells, Na⁺, K⁺-ATPase activity was determined as ouabain-sensitive oxygen consumption (OS Qo₂). Maximal OS Qo₂, measured in Na⁺ loaded cells, was the same in DS and DR rats. The K₀₆ for K⁺ was significantly lower in DS than DR rats (0.163 ±0.042 vs. 0.447 + 0.061 mM, P < 0.05), indicating that factors regulating Na⁺, K⁺-ATPase activity in intact cells are altered in DS rats. Kinetic parameters for Na⁺ activation in cells were the same in both strains. In summary, the function of renal Na⁺, K⁺-ATPase molecule is not altered in DS rats. The intracellular systems that regulate renal Na⁺, K⁺-ATPase activity might be different in DS and DR rats.     

Preferential activation of peripheral blood V gamma 9+ gamma/delta T cells by group A, B and C but not group D or F streptococci.

Previous studies have established that inactivated mycobacteria are potent and selective activators of V gamma 9+/V delta 2+ human gamma/delta T cells. Here we have analysed the proliferative response of human gamma/delta T cells to five serologically distinct groups of streptococci. While heat-inactivated streptococci of all five serogroups tested (A, B, C, D and F) induced a strong proliferative response in peripheral blood mononuclear cells (PBMC), only groups A, B and C elicited a selective activation of V gamma 9+ gamma/delta T cells in 10 (serogroup B) or 11 (serogroups A and C) of 11 tested healthy individuals. In striking contrast, groups D and F streptococci failed to activate gamma/delta T cells in nine of 11 donors and induced only a weak gamma/delta T cell response in two additional individuals. Depletion of V gamma 9+ T cells before culture completely eliminated all gamma/delta T cell responses to streptococci. These data indicate that groups A, B and C (but not D or F) streptococci can be included in the growing list of selective ligands for V gamma 9+/V delta 2+ human gamma/delta T cells.     

An immunohistochemical study of neuronal and glial cell reactions in retinae of rats with experimental glaucoma

Glaucoma is a common disease seen in the eye clinic, but its associated pathological processes, especially the role of glial cells in glaucomatous retinae, are still under debate. The aim of the present work was to study the responses of astrocytes, Müller cells and microglia in retinae of rats with experimental glaucoma. Glaucoma was induced in adult male Wistar rats by cauterizing limbal-derived veins and the changes in glial fibrillary acidic protein (GFAP), OX42, OX18, OX6 and EDI expression were studied by immunohistochemical staining. Neuronal cell viability was studied by immunostaining with the neuronal nuclei (NeuN) antibody. In the experimental glaucomatous eyes, a significant drop in the number of NeuN-positive neurons was observed from 7 days postoperation and beyond in both the ganglion cell layer and inner nuclear layer. The expression of GFAP and OX42 was increased during the first 2 months after operation and reduced in rats at 3 and 4 months. OX6 and OX18 immunoreactivity was induced in some microglia of both glaucomatous and sham-operated control eyes. Possible mechanisms of the reaction of astrocytes, Müller cells and microglia in neuronal degeneration following glaucoma are discussed.     

Epstein-Barr virus in gastric carcinomas with lymphoid stroma

AIMS: To clarify the relationship between the Epstein-Barr virus (EBV) and gastric carcinoma with lymphoid stroma (GCLS) in Koreans, and to characterize the EBV-positive GCLS. METHODS AND RESULTS: EBV infection was examined using EBER in-situ hybridization and polymerase chain reaction in 45 cases of GCLS among Koreans, and in 292 consecutive cases of gastric carcinomas without lymphoid stroma (non-GCLS) as controls. EBV infection was found in 30 tumours (67%) of GCLS and 10 tumours (3.4%) of non-GCLS (P < 0.05). EBV-positive GCLS was more prevalent in males, poorly differentiated histological type and diffuse type in Lauren's classification, and tended to be located more in the middle third of the stomach than EBV-negative GCLS (P < 0.05). p53 overexpression was observed in 22% of GCLS (17% of EBV-positive GCLS and 33% of EBV-negative GCLS), and 34% of non-GCLS (EBV-positive GCLS vs. non-GCLS: P = 0.056). The survival of the patient with GCLS was not correlated with EBV infection or p53 immunoexpression (follow-up period: 11-97 months). CONCLUSIONS: GCLS in Koreans is strongly associated with EBV infection. The prognosis in GCLS is not dependent upon either the status of EBV infection or the status of p53 immunoexpression.     

Requirement of the T cell receptor for antigen presentation by T lymphocytes. Effect of envelope glycoproteins of HIV-1 on antigen presentation by T cells.

We have developed CD4+, tetanus antigen-specific T cell clones that proliferate in the presence of tetanus antigen and autologous irradiated peripheral blood leucocytes (PBL) as antigen-presenting cells (APC). There have been several reports that T cells can present antigen themselves. We have used tetanus antigen-specific T cell clones to examine the effects of envelope glycoproteins of HIV-1 on processing and presentation of antigen to T cells. Cloned T cells were pre-incubated with soluble crude preparation of tetanus antigen for 4 h at 37 degrees C, irradiated, and used as APC (T-APC). These cells could present antigen, as assessed by the ability of the autologous cloned T cells to proliferate. Resting T cells and phytohaemagglutinin-activated T cell blasts from autologous PBL could not present tetanus antigen to the responder cloned T cells. Antigen presentation by T-APC was abrogated by treating cells with anti-HLA-DR but not by anti-HLA-DQ monoclonal antibodies; treatment of tetanus antigen-pulsed T-APC with anti-tetanus antibody also blocked the ability of these cells to induce proliferation in responder T cells. Antigen presentation by cloned T cells was by a chloroquine-resistant pathway. Pretreatment of T-APC with envelope glycoprotein of HIV-1, gp120, did not affect the proliferative responses of the responder T cells. These data suggest that gp120 does not inhibit the antigen-presenting function while suppressing antigen-specific responses.     

Case of postradiation osteosarcoma with a short latency period of 3 years

Osteosarcoma is one of the neoplasms that may occur following exposure to radiation. A case of osteosarcoma arising in the craniofacial bone with a short latency period of 3 years after radiotherapy for maxillary squamous cell carcinoma is described. A 64-year-old-man underwent right partial maxillectomy and chemoradiotherapy due to squamous cell carcinoma of his right maxillary sinus. Histologically, the tumor was composed of moderately differentiated squamous cell carcinoma with a component of spindle cell carcinoma. Three years later, osteosarcoma developed in the craniofacial bone within the irradiation field of the first tumor. Detailed histological examination demonstrated that there was no component of osteosarcoma in the first tumor or squamous cell carcinoma in the second tumor. Radiation-induced osteosarcoma usually occurs after a long latency period of more than 10 years after the radiotherapy. In this case, osteosarcoma was possibly a radiation-induced osteosarcoma with a short latency period of 3 years.