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Inducing antitumor T cell immunity: comparative functional analysis of interstitial versus Langerhans dendritic cells in a human cell line model 总被引:1,自引:0,他引:1
Santegoets SJ Bontkes HJ Stam AG Bhoelan F Ruizendaal JJ van den Eertwegh AJ Hooijberg E Scheper RJ de Gruijl TD 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(7):4540-4549
Dendritic cells (DC) are increasingly applied as a cellular adjuvant in immunotherapy of cancer. Two major myeloid DC subsets are recognized: interstitial DC (IDC) that infiltrate connective tissues and Langerhans cells (LC) that line epithelial surfaces. Yet, functional differences between IDC and LC remain to be defined. We recently showed that the CD34(+) acute myeloid leukemia cell line MUTZ-3 supports differentiation of both DC-SIGN(+) IDC and Langerin-positive Birbeck granule-expressing LC. By comparative functional characterization of MUTZ-3 IDC and MUTZ-3 LC, we aimed to elucidate the relative abilities of these two DC subsets to induce a specific T cell response and reveal the more suitable candidate for use as a clinical vehicle of tumor vaccines. Although mature LC and IDC displayed comparable lymph node-homing potential, mature LC showed higher allogeneic T cell stimulatory capacity. Nevertheless, IDC supported the induction of tumor Ag-specific CD8(+) T cells at an overall higher efficiency. This might be related to the observed inability of LC to release T cell stimulatory cytokines such as IL-12p70, IL-23, and IL-15. Although this inability did not result in a detectable deviation in the cytokine expression profile of primed T cells, transduction with IL-12p70 significantly improved priming efficiency of LC, and ensured a functional equivalence with IDC in this regard. In conclusion, except for the inability of LC to release distinct type 1 T cell stimulatory cytokines, in vitro function of LC and IDC suggests comparable abilities of both subsets for the in vivo induction of antitumor T cells. 相似文献
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Timothy R. D. J. Radstake Lenny van Bon Jasper Broen Mark Wenink Kim Santegoets Yanhui Deng Anila Hussaini Robert Simms William W. Cruikshank Robert Lafyatis 《PloS one》2009,4(6)
Background
Regulatory T cells (Tregs) are essential in the control of tolerance. Evidence implicates Tregs in human autoimmune conditions. Here we investigated their role in systemic sclerosis (SSc).Methods/Principal Findings
Patients were subdivided as having limited cutaneous SSc (lcSSc, n = 20) or diffuse cutaneous SSc (dcSSc, n = 48). Further subdivision was made between early dcSSc (n = 24) and late dcSSc (n = 24) based upon the duration of disease. 26 controls were studied for comparison. CD3+ cells were isolated using FACS and subsequently studied for the expression of CD4, CD8, CD25, FoxP3, CD127, CD62L, GITR, CD69 using flow cytometry. T cell suppression assays were performed using sorted CD4CD25highCD127- and CD4CD25lowCD127high and CD3+ cells. Suppressive function was correlated with CD69 surface expression and TGFβ secretion/expression. The frequency of CD4+CD25+ and CD25highFoxP3highCD127neg T cells was highly increased in all SSc subgroups. Although the expression of CD25 and GITR was comparable between groups, expression of CD62L and CD69 was dramatically lower in SSc patients, which correlated with a diminished suppressive function. Co-incubation of Tregs from healthy donors with plasma from SSc patients fully abrogated suppressive activity. Activation of Tregs from healthy donors or SSc patients with PHA significantly up regulated CD69 expression that could be inhibited by SSc plasma.Conclusions/Significance
These results indicate that soluble factors in SSc plasma inhibit Treg function specifically that is associated with altered Treg CD69 and TGFβ expression. These data suggest that a defective Treg function may underlie the immune dysfunction in systemic sclerosis. 相似文献3.
Mijia Lu Yuexiu Zhang Piyush Dravid Anzhong Li Cong Zeng Mahesh KC Sheetal Trivedi Himanshu Sharma Supranee Chaiwatpongsakorn Ashley Zani Adam Kenney Chuanxi Cai Chengjin Ye Xueya Liang Jianming Qiu Luis Martinez-Sobrido Jacob S. Yount Prosper N. Boyaka Shan-Lu Liu Mark E. Peeples Amit Kapoor Jianrong Li 《Journal of virology》2021,95(20)
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Dukka B KC 《BMC structural biology》2009,9(1):12-9
Background
Common structural biology methods (i.e., NMR and molecular dynamics) often produce ensembles of molecular structures. Consequently, averaging of 3D coordinates of molecular structures (proteins and RNA) is a frequent approach to obtain a consensus structure that is representative of the ensemble. However, when the structures are averaged, artifacts can result in unrealistic local geometries, including unphysical bond lengths and angles. 相似文献5.
Plasmonics - This study shows development of highly sensitive and stable localized surface plasmon resonance (LSPR)-active U-bent glass and polymeric optical fiber (GOF and POF) sensor probes by a... 相似文献
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We report a high-sensitivity cell secretome detection method using competitive immuno-aggregation and a micro-Coulter counter. A target cell secretome protein competes with anti-biotin-coated microparticles (MPs) to bind with a biotinylated antibody (Ab), causing decreased aggregation of the functionalized MPs and formation of a mixture of MPs and aggregates. In comparison, without the target cell secretome protein, more microparticles are functionalized, and more aggregates are formed. Thus, a decrease in the average volume of functionalized microparticles/aggregates indicates an increase in cell secretome concentration. This volume change is measured by the micro-Coulter counter, which is used to quantitatively estimate the cell secretome concentration. Vascular endothelial growth factor (VEGF), one of the key cell secretome proteins that regulate angiogenesis and vascular permeabilization, was used as the target protein to demonstrate the sensing principle. A standard calibration curve was generated by testing samples with various VEGF concentrations. A detection range from 0.01 ng/mL to 100.00 ng/mL was achieved. We further demonstrated the quantification of VEGF concentration in exogenous samples collected from the secretome of human mesenchymal stem cells (hMSCs) at different incubation times. The results from the assay agree well with the results of a parallel enzyme-linked immunoabsorbent assay (ELISA) test, indicating the specificity and reliability of the competitive immuno-aggregation assay. With its simple structure and easy sample preparation, this assay not only enables high sensitivity detection of VEGF but also can be readily extended to other types of cell secretome analysis as long as the specific Ab is known. 相似文献
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Wolfgang Lutz Samir KC 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1554):2779-2791
The total size of the world population is likely to increase from its current 7 billion to 8–10 billion by 2050. This uncertainty is because of unknown future fertility and mortality trends in different parts of the world. But the young age structure of the population and the fact that in much of Africa and Western Asia, fertility is still very high makes an increase by at least one more billion almost certain. Virtually, all the increase will happen in the developing world. For the second half of the century, population stabilization and the onset of a decline are likely. In addition to the future size of the population, its distribution by age, sex, level of educational attainment and place of residence are of specific importance for studying future food security. The paper provides a detailed discussion of different relevant dimensions in population projections and an evaluation of the methods and assumptions used in current global population projections and in particular those produced by the United Nations and by IIASA. 相似文献
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Michael?B?Kupper Michael?Huhn Holger?Spiegel Julian?KC?Ma Stefan?Barth Rainer?Fischer Ricarda?FinnernEmail author 《BMC biotechnology》2005,5(1):4