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T cell activation is enhanced by the costimulatory interaction of B7 on antigen-presenting cells and CD28 on T cells, resulting
in long-term T cell proliferation, differentiation and production of large amounts of cytokines, such as interleukin (IL)-2.
CTLA-4 is a co-stimulation receptor that shares 31% homology with CD28 and binds B7 family members with higher affinity. CTLA-4
is transiently expressed intracellularly and on the cell surface following activation of T cells. We have studied the kinetics
of CTLA-4 expression and the effects of dexamethasone on CTLA-4 expression during T cell activation in cultures of mouse spleen
cells stimulated by a mixture of immobilized anti-CD3 and anti-CD28 monoclonal antibodies (anti-CD3/CD28 mAb) or concanavalin
A (ConA). CTLA-4 expression peaked on day 2 and returned to background levels after 7 days. Dexamethasone was found to potentiate
CTLA-4 expression in a dose-dependent manner with an EC50 effective concentration 50%) of about 10−8 M. In contrast, other immunosuppressive agents, such as rapamycin or cyclosporin A had no or an inhibitory effect on CTLA-4
expression, respectively. Dexamethasone also stimulated CD28 expression, but inhibited IL-2R expression during anti-CD3/CD28
mAb-induced mouse splenic T cell activation. Western blot analyses of lysates of activated mouse T cells showed that dexamethasone
increased CTLA-4 protein levels twofold during anti-CD3/CD28 mAb-induced activation. Dexamethasone also enhanced CTLA-4 messenger
RNA twofold as quantified by ribonuclease protection assay. The effects of dexamethasone on CTLA-4 expression were glucocorticoid-specific
and completely inhibited by the glucocorticoid receptor antagonist mifepristone (RU486), indicating that the effect of dexamethasone
on CTLA-4 expression is mediated through the glucocorticoid receptor. In conclusion, the immunosuppressive agent dexamethasone
actually stimulates CTLA-4 expression, which is involved in downregulation of T cell activation.
Received 19 May 1999; received after revision 13 July 1999; accepted 13 July 1999 相似文献
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M. Gasser H. Bilger K-D. Hofmann K. Miescher 《Cellular and molecular life sciences : CMLS》1959,15(2):52-53
Summary Development of a spectral colour integrator enabling to reproduce on a screen any colour up to the theoretical limits and
to determine quantitatively important notions of colour metric.
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A Trumpp Y Refaeli T Oskarsson S Gasser M Murphy G R Martin J M Bishop 《Nature》2001,414(6865):768-773
Overexpression of the proto-oncogene c-myc has been implicated in the genesis of diverse human tumours. c-Myc seems to regulate diverse biological processes, but its role in tumorigenesis and normal physiology remains enigmatic. Here we report the generation of an allelic series of mice in which c-myc expression is incrementally reduced to zero. Fibroblasts from these mice show reduced proliferation and after complete loss of c-Myc function they exit the cell cycle. We show that Myc activity is not needed for cellular growth but does determine the percentage of activated T cells that re-enter the cell cycle. In vivo, reduction of c-Myc levels results in reduced body mass owing to multiorgan hypoplasia, in contrast to Drosophila c-myc mutants, which are smaller as a result of hypotrophy. We find that c-myc substitutes for c-myc in fibroblasts, indicating they have similar biological activities. This suggests there may be fundamental differences in the mechanisms by which mammals and insects control body size. We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size. 相似文献
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Summary No qualitative differences have been found between the electrophoretic protein patterns observed in normal and in aneuploid embryos ( 3n × 2n). The overall amount of extractable protein increases, however, less rapidly in aneuploid than in normal embryos. 相似文献
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Zusammenfassung Die Tumoranfälligkeit von Hamstern, die am Ende der ersten Lebenswoche eine Injektion von Adenovirus Typus 12 erhielten, wurde erhöht, wenn den Tieren unmittelbar nach der Geburt der Thymus entfernt worden war. Die bei der gewählten Virusdosis erzeugte Tumorträgerrate von 40% bei scheinoperierten Kontrolltieren stieg nach neonataler Thymektomie auf 90%, bei Weibchen allein auf 100% an.
Herrn Prof. Dr.A. Werthemann zum 70. Geburtstag gewidmet. 相似文献
Herrn Prof. Dr.A. Werthemann zum 70. Geburtstag gewidmet. 相似文献