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51.
Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells 总被引:29,自引:0,他引:29
Zuany-Amorim C Sawicka E Manlius C Le Moine A Brunet LR Kemeny DM Bowen G Rook G Walker C 《Nature medicine》2002,8(6):625-629
Allergic asthma is a chronic inflammatory disease and despite the introduction of potent and effective drugs, the prevalence has increased substantially over the past few decades. The explanation that has attracted the most attention is the 'hygiene hypothesis', which suggests that the increase in allergic diseases is caused by a cleaner environment and fewer childhood infections. Indeed, certain mycobacterial strains can cause a shift from T-helper cell 2 (Th2) to Th1 immune responses, which may subsequently prevent the development of allergy in mice. Although the reconstitution of the balance between Th1 and Th2 is an attractive theory, it is unlikely to explain the whole story, as autoimmune diseases characterized by Th1 responses can also benefit from treatment with mycobacteria and their prevalence has also increased in parallel to allergies. Here we show that treatment of mice with SRP299, a killed Mycobacterium vaccae-suspension, gives rise to allergen-specific CD4+CD45RB(Lo) regulatory T cells, which confer protection against airway inflammation. This specific inhibition was mediated through interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), as antibodies against IL-10 and TGF-beta completely reversed the inhibitory effect of CD4+CD45RB(Lo) T cells. Thus, regulatory T cells generated by mycobacteria treatment may have an essential role in restoring the balance of the immune system to prevent and treat allergic diseases. 相似文献
52.
Demissie A Abebe M Aseffa A Rook G Fletcher H Zumla A Weldingh K Brock I Andersen P Doherty TM;VACSEL Study Group 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(11):6938-6943
The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes "protective immunity" is one of the holy grails of M. tuberculosis immunology. It is known that IFN-gamma is essential for protection, but it is also apparent that IFN-gamma levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4delta2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response. 相似文献
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Tuberculosis is out of control in developing countries, where it is killing millions of people every year. In these areas, the present vaccine - Mycobacterium bovis bacillus Calmette-Guérin (BCG) - is failing. Progressive tuberculosis occurs because the potentially protective T helper 1 (T(H)1)-cell response is converted to an immunopathological response that fails to eliminate the bacteria. Here, we discuss the data indicating that the problem in developing countries is not a lack of adequate T(H)1-cell responses but, instead, an exaggerated tendency to switch to immunopathological responses. We propose that a successful vaccine needs to block this immunopathology, because it is not the quantity of T(H)1-cell activity that matters but, rather, its context. 相似文献
55.
Are we sparing the dirt and spoiling our children's immune systems? The theory that some germs are necessary in developing healthy immune systems is gaining credence as more evidence emerges. It is vital that we find out which germs are needed, when and how, before the increase in diseases attributable to faulty regulation of the immune system (allergies, autoimmunity, inflammatory bowel disease) spirals out of control. 相似文献
56.
Michiel van der Flier Dyana B. Sharma Silvia Estev?o Marieke Emonts Denise Rook Jan A. Hazelzet Johannes B. van Goudoever Nico G. Hartwig 《PloS one》2013,8(7)
The co-inhibitory immune receptor carcinoembryonic antigen-related cell-adhesion molecule 1 (CEACAM1) and its self-ligand CEACAM1 can suppress T cell function. Suppression of T cell function in sepsis is well documented. Late-onset neonatal sepsis in VLBW-infants was associated with an increased percentage CEACAM1 positive CD4+ T-cells. Meningococcal septic shock in children was associated with increased serum soluble CEACAM1. In conclusion our data demonstrate increased surface expression of the co-inhibitory immune receptor CEACAM1 in late-onset neonatal sepsis in VLBW-infants, and increased circulating soluble CEACAM1 in children with meningococcal sepsis. Increased T-cell CEACAM1 expression and increased circulating soluble CEACAM1 may contribute to sepsis-associated immune suppression. 相似文献
57.
A.D. Khosravi J.L. Stanford H.D. Donoghue & G.A.W. Rook 《Journal of applied microbiology》1997,83(5):596-602
The purpose of this study was to identify Mycobacterium scrofulaceum reliably and rapidly and investigate diversity within the species. Fifty-four cultures were identified as Myco. scrofulaceum by preliminary cultural and biochemical tests, thin-layer chromatography and double diffusion. These strains were examined by PCR based on the 65 kDa heat stress protein gene, followed by restriction enzyme analysis of the product with Bst EII and Hae III. This produced seven groups, most with fewer fragments than had been reported previously. The technique was a rapid and reliable method for studying variation within Myco. scrofulaceum but alone, was unable to discriminate between some of these variants and other genetically similar species. When PCR-RFLP results were combined with biochemical tests, the major groups appeared to relate to different disease situations and thus, may have some epidemiological value. 相似文献
58.
Journal of Mammalian Evolution - The late Miocene was a period of great radiation for the subfamily Caninae in North America. During this time, the early taxa of the two tribes of this subfamily,... 相似文献
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Adipose tissue-derived stem cells (ADSCs) are one population of adult stem cells that can self renew and differentiate into
multiple lineages. Because of advantages in method and quantity of acquisition, ADSCs are gaining attention as an alternative
source of bone marrow mesenchymal stem cells. In this study, we performed microRNA profiling of undifferentiated and of neurally-differentiated
ADSCs to identify the responsible microRNAs in neurogenesis using this type of stem cell. MicroRNAs from four different donors
were analysed by microarray. Compared to the undifferentiation control, we identified 39–101 microRNAs with more than two-fold
higher expression and 3–9 microRNAs with two-fold lower expression. The identified microRNAs were further analysed in terms
of gene ontology (GO) in relation with neurogenesis, based on their target mRNAs predicted by computational analysis. This
study revealed the specific microRNAs involved in neurogenesis via microRNA microarray, and may provide the basic information
for genetic induction of adult stem cell differentiation using microRNAs. 相似文献