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61.
Two cytokines IL-4 and IL-12 are known to determine the balance between T(h)1 and T(h)2 development. In addition to IL-4 production of V(alpha)14(+) NKT cells, they have recently been demonstrated to have the capacity to stimulate IL-12 production by antigen-presenting cells (APC). This study demonstrates that IFN-gamma is absolutely required for the NKT cell-stimulated IL-12 production. Culture of B cell-depleted spleen cells from C57BL/6 mice with alpha-galactosylceramide (alpha-GalCer) capable of selectively stimulating V(alpha)14/J(alpha)281(+) NKT cells resulted in the production of IL-12 together with IL-4. Whereas IL-4 production occurred in culture of IFN-gamma(-/-) C57BL/6 splenocytes, the same culture failed to generate IL-12 production. While IL-12 production induced during culture of V(alpha)14(+) NKT cells and APC depended on the interaction between CD40 ligand on NKT cells and CD40 on APC, the expression levels of these key molecules were comparable in cells from wild-type and IFN-gamma(-/-) mice. Addition of rIFN-gamma to alpha-GalCer stimulated IFN-gamma(-/-) splenocyte culture, and administration of rIFN-gamma to alpha-GalCer-injected IFN-gamma(-/-) mice resulted in the restoration of IL-12 production in vitro and in vivo. These results illustrate a mandatory role for IFN-gamma in V(alpha)14(+) NKT cell-stimulated IL-12 production by APC. 相似文献
62.
The occurrence of pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 29-32 kd insulin-like growth factor binding protein, now termed type 1 or IGF-bp1, has been examined in the human ovary by monoclonal and polyclonal antibody based radioimmunoassay and immunohistological techniques. Follicular fluids aspirated from 51 follicles of 32 women undergoing hyperstimulation involving buserelin or clomiphene-based protocols contained 35.5-276.0 ng/ml (mean 101.0 mg/ml) of immunoreactive IGF-bp1. Mean fluid concentrations were three times the level of IGF-bp1 detected in paired serum samples, available for 21 women. Immunoreactive IGF-bp1 in follicular fluid exhibited similar dose-response curves to purified protein and amniotic fluid and immunoreactive IGF-bp1 coeluted in gel filtration with a peak of [125I]-IGF-1 binding corresponding to the elution profile of purified IGF-bp1. Gel filtration also revealed the presence in follicular fluid of a greater than 100 kd binding protein with a binding capacity equal to IGF-bp1 under the conditions employed. A highly significant correlation (P less than 0.001) was found between follicular fluid progesterone and IGF-bp1 and a correlation of lower significance was found between oestradiol and IGF-bp1 (P less than 0.05). However, only low levels of immunoreactive IGF-bp1 were detected in supernatant media of granulosa cells in culture (range undetectable to 2.3 ng/ml). Employing monoclonal antibody-based immunohistology, immunoreactive IGF-bp1 was consistently associated with luteinized granulosa cells of corpora lutea rather than paraluteal cells and its intensity of reactivity appeared to reflect luteal phase steroid hormone profiles. No consistent reactivity was detected in preovulatory follicles and granulosa cells in culture, although reactivity was associated with primordial oocytes. Immunoreactive IGF-bp1 was detected in six of nine supernatant media of explants of luteal tissue obtained from five corpora lutea, with levels ranging from undetectable to greater than 200 ng/ml. These observations suggest that IGF-bp1 is primarily related to luteinization of the granulosa and the resultant luteal cells, and if produced by the luteal cells, additional exogenous factors are required to induce production by granulosa cells in vitro. 相似文献
63.
Guomei Tang Huijun Xie Lin Xu Yixin Hao Dayu Lin Daming Ren 《American journal of medical genetics. Part A》2002,114(4):446-449
Several lines of evidence have suggested some common genetic risk factors for Alzheimer disease (AD) and Parkinson disease (PD) because there are some overlapping pathologies in these two neurodegenerative diseases. In the present study, we investigated the role of Apolipoprotein E gene polymorphism and the signal peptide polymorphism in alpha‐1 antichymotrypsin (ACT) gene in idiopathic sporadic PD. The study was performed in a sample consisting of 68 PD cases and 160 healthy subjects in Shanghai China. We found no significant differences of ACT gene polymorphic distribution between PD cases and controls. The ApoE gene ε2/ε4 genotype was significantly more frequent in PD subjects (χ2 = 7.126, df = 1, P = 0.008) and conferred a 12.70 times susceptibility for PD (OR = 12.62, 95% CI: 1.445–110.17, χ2 = 5.259, P < 0.05, AF = 4.59%). No interaction of ApoE and ACT genes was detected in PD. Therefore, our data suggested that the ApoE ε2/ε4 genotype might be a susceptibility variant of moderate effect for sporadic idiopathic PD in our samples, whereas the ACT gene signal peptide polymorphism might not. © 2002 Wiley‐Liss, Inc. 相似文献
64.
Hussain R Shiratsuchi H Phillips M Ellner J Wallis RS 《Clinical and experimental immunology》2001,123(2):210-218
Cachexia is one of the prominent features of advanced tuberculosis (TB) seen in association with increased expression of the monokine TNF-alpha. Several mycobacterial proteins, including PPD, stimulate TNF-alpha secretion from monocytes. Host factors that may play a role in cytokine expression from monocytes remain largely unknown. One such factor is the opsonizing antibodies. Monocytes have high-affinity receptors (FcgammaI and FcgammaIII) for IgG1 and IgG3 antibodies that mediate antigen uptake. We have reported selective up-regulation of IgG1 (which bind to Fcgamma receptors) in advanced TB and have recently shown the ability of PPD-specific IgG1 antibodies to augment TNF-alpha expression in PPD-stimulated monocytes. These observations have now been extended to other cytokines with semipurified fractions from secreted antigens of Mycobacterium tuberculosis (containing 30 kD and 58 kD) that were devoid of lipids, glycolipids and carbohydrates. In the presence of heat-inactivated TB plasma containing known amounts of antigen-specific IgG1 antibodies, these fractions induced significantly increased TNF-alpha, IL-6 and IL-10 secretion. Absorption of IgG1 with Protein 'A' removed the augmenting activity for TNF-alpha and IL-6 secretion from the TB plasma samples. In the case of IL-10, removal of IgG1 resulted in increased rather than decreased IL-10 secretion. These results suggest a possible pathogenic role for antibodies in TB by enhancing proinflammatory and blocking down-regulatory cytokines such as IL-10 cytokines during the chronic phase of TB. 相似文献
65.
de la Hera Antonio; Marston Wendy; Aranda Crisanto; Toribio Marie-Luisa; Martinez-A. Carlos 《International immunology》1989,1(5):471-478
Development of the T cell lineage is characterized by the homingof hematopoietic precursors to thymus, followed by their acquisitionof receptors for antigen. T cell receptors are alpha.gif" ALT="{alpha}" BORDER="0">ß or heterodimers associated with CD3 (TCR-CD3). Very early T cellprecursors in humans have been characterized as CD7+45+ cellswhich lack the T cell differentiation antigens CD1, CD2, CD3,CD4, and CD8. A phenotypically equivalent early thymocyte populationalso occurs in postnatal life, and we have previously shownthat interleukin 2 (IL2) promotes the development in vitro ofboth the alpha.gif" ALT="{alpha}" BORDER="0">ß and the T cells from these early thymocytes.Here we have analyzed the requirements of the induction of theIL2 pathway in early thymocytes, and their developmental potential.We show that: (I) thymic stromal cells, which are present inthymocyte suspensions, are necessary to induce the IL2 pathwayand the development of alpha.gif" ALT="{alpha}" BORDER="0">ß or T cell lineages fromearly thymocytes in vitro; and (II) when removed from the invivo environment, early thymocytes can develop in vitro intoTCR-CD3– cells of the natural killer (NK) lineage. Weconclude that CD7+45+, CD1–2–3–4–8–early thymocytes are multipotential progenitors that, at least,have the capacity to develop into alpha.gif" ALT="{alpha}" BORDER="0">ß or T cell andNK lineages. The analysis of the mechanisms of generation andselection of human T and NK cell diversity, not feasible inbone marrow cultures, is now possible. 相似文献
66.
Waanders Gary A.; Lussow Alexander R.; MacDonald H. Robson 《International immunology》1993,5(1):55-61
Reactivity of murine T cells with viral or bacterial superantigensis clearly correlated with the expression of TCR Vßdomains. Thus, T cells responding to the minor lymphocyte stimulatorylocus (Mls-1a) or staphylococcal enterotoxin B (SEB) expresspredominantly TCR Vß6 or Vß8.2 respectively.We have investigated the involvement of the other major variableelement of the TCR, the Valpha.gif" ALT="{alpha}" BORDER="0"> domain, in these superantigen responses.Using a panel of anti-TCR Valpha.gif" ALT="{alpha}" BORDER="0"> mAbs, It is demonstrated that theTCR Valpha.gif" ALT="{alpha}" BORDER="0"> repertoire among superantigen stimulated Vß6+or Vß8.2+ blasts (responding to Mls-1a or SEB respectivelyin vitro) is altered in comparison with anti-CD3 stimulatedcells expressing the same Valpha.gif" ALT="{alpha}" BORDER="0"> domains. Furthermore, the TCR Valpha.gif" ALT="{alpha}" BORDER="0">repertoire is strongly skewed in TCR Vß8.2 transgenicmice that have undergone extensive peripheral clonal deletionafter SEB injection. These data imply that the Valpha.gif" ALT="{alpha}" BORDER="0"> domain influencessuperantigen recognition by sthe TCR. 相似文献
67.
Maeda Toshiro; Devens Bruce H.; Fukuse Satoshi; Turck Christoph; Webb David R. 《International immunology》1995,7(8):1339-1351
Previous studies of the TCRalpha.gif" ALT="{alpha}" BORDER="0"> chain gene have located promoterelements 5' to the start of the various Valpha.gif" ALT="{alpha}" BORDER="0"> genes. The only fullycharacterized enhancer for the entire alpha.gif" ALT="{alpha}" BORDER="0"> chain gene (V, J andC genes) has been located {small tilde}3 kb from the 3' endof Calpha.gif" ALT="{alpha}" BORDER="0">. We now report the existence of additional regulatory elementslocated in the introns of several murine Valpha.gif" ALT="{alpha}" BORDER="0"> genes (Valpha.gif" ALT="{alpha}" BORDER="0">1, Valpha.gif" ALT="{alpha}" BORDER="0">3 andValpha.gif" ALT="{alpha}" BORDER="0">B6.2.16). In the case of Valpha.gif" ALT="{alpha}" BORDER="0">1, this element appears to be a promoterwith bidirectional activity that is not T cell specific. Interestingly,upstream of the promoter in the antisense strand, an open readingframe has been found that codes for a small molecular weightprotein ({small tilde}60 amino acids) that contains a prollne-richregion and a tyrosine-isoleucine motif that has homology toIgß (the B29 gene product). A rabbit antiserum madeagainst this sequence has confirmed its existence by Westernblot and immunoprecipitation. Thus this Valpha.gif" ALT="{alpha}" BORDER="0">1 intronic promoterhas the potential not only to induce the formation of a truncatedValpha.gif" ALT="{alpha}" BORDER="0">1 gene product, but also regulates the expression of a smallmolecular weight protein that may be involved in lymphocyteantigen receptor signaling. The activity of this promoter isregulated by changes in intracellular calcium. In the presenceof ionomycin the promoter is down-regulated in the sense directionand its activity is enhanced in the antisense direction. Thisresult suggests that this promoter can act differentially toproduce two very different gene products. The bidirectionalValpha.gif" ALT="{alpha}" BORDER="0">1 promoter appears to be the first in the Ig superfamily toinduce potentially functional proteins in both directions. 相似文献
68.
Demaison Christophe; Chastagner Patricia; Moreau Jean-Louis; Theze Jacques 《International immunology》1996,8(10):1521-1528
The IL-2 receptor (IL-2R) is composed of three chains a, ßand . In mice, contrary to the human system, we have previouslydemonstrated that the IL-2Rß complex does not bindIL-2. Therefore, mouse IL-2 response is completely dependenton the expression of the IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> gene product. T cell clones expressingmouse IL-2Rß and the human IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> transgene have beenstudied. When cells are grown in IL-4, mouse IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> is not expressed.However, exposure to IL-2 leads to the expression of the endogenousmurine IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> subunit. The T cell line expressing mouse IL-2Rand human IL-2Rß can grow in IL-2 but does not expressendogenous murine IL-2 Ralpha.gif" ALT="{alpha}" BORDER="0">. Transfection of these cells with thehuman IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> gene restores the capacity to induce murine IL-2Ralpha.gif" ALT="{alpha}" BORDER="0">.This result demonstrates that IL-2-IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> interactions are requiredfor induction of IL-2Ralpha.gif" ALT="{alpha}" BORDER="0">. The kinetics of induction and deinductionof murine IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> have been studied using clone 18.III. From negativecells, expression of murine IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> is a very slow phenomenon.From cells fully expressing IL-2Ralpha.gif" ALT="{alpha}" BORDER="0">, deinduction is a two-stepprocess: after a rapid decrease of IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> the cells continueto express, for a long period of time, basal levels of murineIL-2Ralpha.gif" ALT="{alpha}" BORDER="0">. When cells expressing basal levels of IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> are exposedto IL-2, induction of IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> is a very rapid phenomenon. Theautoregulatory loop formed by IL-2-IL-2Ralpha.gif" ALT="{alpha}" BORDER="0"> therefore displaysdifferent levels of functioning. 相似文献
69.
70.
为进一步探讨肝硬化患者上消化道出血的发生机制及病理生理意义,采用ELISA方法分别定量测定40例肝硬化患者与10例对照组患者血浆血栓素B2(TXB2)、6-酮-前列腺素F1α(6-酮-PGF1α)及血管性假血友病因子(vWF)的水平。结果显示:肝硬化患者无上消化道出血组血浆TXB2水平、TXB2/6酮-PGF1α比值较对照组明显降低(P<0.05),较出血组显著增高(P<0.05或0.01);而血浆6-酮-PGF1α与vWF水平较对照组明显增高(P<0.05或0.01),较出血组显著降低(P<0.05)。结果表明,肝硬化患者上消化道出血与血浆TXB2下降、6-酮-PGF1α升高及其比例衡有密切关系,vWF水平升高能反映肝硬化血管内皮损伤及上消化道出血倾向。 相似文献