Supraphysiological levels of IL-7 induce increase counts of pre-B cells, naive T cells and memory phenotype CD8+ T cells. Immunocomplexes of IL-7 and αIL-7 mAb M25 (IL-7/M25) were described as IL-7 superagonist in vivo. Thus, treatment of mice with IL-7/M25 remarkably increases the size of the T cell pool. We decided to use IL-7/M25 in order to expand the T cell population prior to the administration of αCTLA-4 and αPD-1 mAbs in tumor-bearing mice and in turn boost the immunotherapy based on a combination of CTLA-4 and PD-1 blockage. We found that just four doses of IL-7/M25 increased the absolute numbers of splenocytes approximately fivefold and significantly shifted the CD4+:CD8+ T cell ratio in favor of CD8+ T cells. There was also a substantive increase in relative counts of memory phenotype CD8+ T cells (approximately threefold) within CD8+ T cells but a significant decrease (approximately 30%) in relative counts of Treg cells within CD4+ T cells. All these data suggest that IL-7/M25 offer a suitable approach to potentiate tumor immunotherapy through CTLA-4 and PD-1 blockage. Unexpectedly, IL-7/M25 significantly abrogated the antitumor activity of αCTLA-4 plus αPD-1 mAbs in the following mouse tumor models: MC-38 and CT26 colon carcinoma and B16F10 melanoma. This paradoxical effect of IL-7/M25 on the antitumor activity of CTLA-4 and PD-1 blockage was not mediated via either increased levels of IL-10 or TGF-β in the sera or increased counts of IL-10-producing B or T cells in the spleen of mice injected with IL-7/M25. Thus, our work shows that caution should be exercised when combining two immunotherapy approaches together.

• MeSH
• antigen CTLA-4 imunologie   MeSH
• antigeny CD279 imunologie   MeSH
• antitumorózní látky imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• imunoterapie metody   MeSH
• interleukin-10 imunologie   MeSH
• interleukin-7 imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom imunologie   MeSH
• modely nemocí na zvířatech MeSH
• monoklonální protilátky imunologie   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory tračníku imunologie   MeSH
• regulační T-lymfocyty imunologie   MeSH
• transformující růstový faktor beta imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The tapeworm Hymenolepis diminuta is a model for the impact of helminth colonization on the mammalian immune system and a candidate therapeutic agent for immune mediated inflammatory diseases (IMIDs). In mice, H. diminuta protects against models of inflammatory colitis by inducing a strong type 2 immune response that is activated to expel the immature worm. Rats are the definitive host of H. diminuta, and are colonized stably and over long time periods without harming the host. Rats mount a mild type 2 immune response to H. diminuta colonization, but this response does not generally ameliorate colitis. Here we investigate the ability of different life cycle stages of H. diminuta to protect rats against a model of colitis induced through application of the haptenizing agent dinitrobenzene sulphonic acid (DNBS) directly to the colon, and monitor rat clinical health, systemic inflammation measured by TNFα and IL-1β, and the gut microbiota. We show that immature H. diminuta induces a type 2 response as measured by increased IL-4, IL-13 and IL-10 expression, but does not protect against colitis. In contrast, rats colonized with mature H. diminuta and challenged with severe colitis (two applications of DNBS) have lower inflammation and less severe clinical symptoms. This effect is not related the initial type 2 immune response. The gut microbiota is disrupted during colitis and does not appear to play an overt role in H. diminuta-mediated protection.

• MeSH
• benzensulfonáty MeSH
• Hymenolepis diminuta fyziologie   MeSH
• interleukin-10 imunologie   MeSH
• interleukin-13 imunologie   MeSH
• interleukin-4 imunologie   MeSH
• kolitida chemicky indukované   imunologie   prevence a kontrola   MeSH
• kolon MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• stadia vývoje MeSH
• Th2 buňky imunologie   MeSH
• zánět imunologie   parazitologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Porcine cytomegalovirus (PCMV) causes lifelong latent infections in swine. The pathogen is occasionally associated with inclusion body rhinitis and pneumonia in piglets, reproductive disorders in pregnant sows and respiratory disease complex in older pigs. Immunosuppressive potential of PCMV infection is discussed. Macrophages were recognised as one of target cell types where propagation of virus occurs. The aim of present study was to set up model PCMV infection of monocyte derived macrophages (MDMs) in vitro for PCMV immunobiology research. Obtained results showed that PCMV is able to infect and propagate in MDMs. Possible immunosuppressive effect of PCMV on infected macrophages was evaluated by measurement of immune relevant gene expression in MDMs. Infection decreased expression of IL-8 and TNF-α (pro-inflammatory cytokines) and increased expression of IL-10 (anti-inflammatory cytokine) on mRNA transcription level. Obtained data support hypothesis that higher sensitivity of animals to coinfection with other swine pathogens and its more severe clinical manifestations could potentially be the consequence of PCMV infection.

• MeSH
• cytokiny imunologie   MeSH
• cytomegalovirové infekce imunologie   veterinární   MeSH
• Cytomegalovirus fyziologie   MeSH
• exprese genu imunologie   MeSH
• interleukin-10 imunologie   MeSH
• interleukin-8 imunologie   MeSH
• makrofágy imunologie   virologie   MeSH
• nemoci prasat imunologie   virologie   MeSH
• prasata MeSH
• přirozená imunita MeSH
• TNF-alfa imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Beneficial effect of maternal milk is acknowledged, but there is still question whether maternal milk from allergic mother is as good as from healthy one. In our study, we have assayed the effect of cells from colostrum of healthy and allergic mothers on gene expression of cytokines in cord blood cells of newborns of healthy and allergic mothers. Cytokines typical for Th1 (IL-2, IFN-gamma), Th2 (IL-4, IL-13), Tregs (IL-10, TGF-beta), and IL-8 were followed. We were not able to detect significant influence of colostral cells on gene expression of cytokines in cord blood after 2-day coculture using Transwell system. There was no difference in gene expression of cytokines in nonstimulated cord blood cells of newborns of healthy and allergic mothers, but generally increased gene expression of cytokines except IL-10 and TGF-beta after polyclonal stimulation was detected in cord blood cells of children of allergic mothers. There was no difference in IL-10 expression in stimulated cord blood cells of children of healthy and allergic mothers. Gene expression of TGF-beta was even decreased in stimulated cord blood cells of children of allergic mothers in comparison to healthy ones. We have not observed difference in the capacity of colostral cells of healthy and allergic mothers to influence gene expression of cytokines in cord blood cells, but we have described difference in the reactivity of cord blood cells between children of allergic and healthy mothers.

• MeSH
• alergie krev   genetika   imunologie   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• exprese genu MeSH
• fetální krev chemie   imunologie   MeSH
• interleukin-10 genetika   imunologie   MeSH
• interleukin-13 krev   MeSH
• interleukin-4 krev   MeSH
• kojenec MeSH
• kolostrum chemie   imunologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• Th1 buňky imunologie   MeSH
• Th2 buňky imunologie   MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dítě MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• humorální imunita MeSH
• idiopatické střevní záněty epidemiologie   genetika   imunologie   MeSH
• incidence MeSH
• interleukin-10 imunologie   MeSH
• interleukiny imunologie   MeSH
• lidé MeSH
• receptor DcR3 imunologie   MeSH
• signální transdukce MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH

Probiotics are believed to prevent or reduce allergy development but the mechanism of their beneficial effect is still poorly understood. Immune characteristics of regulatory T cells (Tregs) in peripheral blood of perinatally probiotic-supplemented children of allergic mothers (51 children), non-supplemented children of allergic mothers (42 children), and non-supplemented children of healthy mothers (28 children) were compared at the age of 6-7 years. A first dose of a probiotic Escherichia coli strain (E. coli O83:K24:H31) was administered within 2 days after the birth and then 12 times during the first months of life and children were followed longitudinally. Proportion and functional properties of Tregs were estimated by flow cytometry in relation to the children's allergy status. Proportion of Tregs in the peripheral blood of children suffering from allergy tends to be higher whereas median of fluorescence intensity (MFI) of FoxP3 was significantly decreased in allergic group. Intracellular presence of regulatory cytokine interleukin (IL)-10 was also lower in allergic children. Immune functions of Tregs reflected by both MFI of FoxP3 and IL-10 in the group of probiotic-supplemented children of allergic mothers were nearly comparable with children of healthy mothers while probiotic non-supplemented children of allergic mothers have decreased immune function of Tregs. Supplementation by probiotic E. coli strain decreases allergy incidence in high-risk children. In contrast to our expectation, proportion of Tregs has not been increased in probiotic supplemented children. Beneficial effect of probiotics on newborn immature immune system could be, at least partially, explained by the modulating immune function of Tregs. In summary, we detected increased proportion of Tregs in peripheral blood of allergic children, their functional properties were decreased in comparison with the Tregs of healthy children. A unifying hypothesis for these findings is that Treg numbers in allergic children are increased in order to compensate for decreased function.

• MeSH
• alergie prevence a kontrola   MeSH
• cytokiny krev   imunologie   MeSH
• dítě MeSH
• Escherichia coli * MeSH
• interleukin-10 krev   imunologie   MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• probiotika aplikace a dávkování   MeSH
• průtoková cytometrie MeSH
• regulační T-lymfocyty imunologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The immunoregulatory properties of mesenchymal stem cells (MSCs) have been well documented in various models in vitro and in vivo. Furthermore, a population of regulatory B cells (Bregs) that produce relatively high concentrations of IL-10 has been recently described. To study the relationship between MSCs and Bregs, we analyzed the effects of MSCs on IL-10 production by lipopolysaccharide (LPS)-activated mouse B cells. The production of IL-10 by B cells remained preserved in the presence of MSCs and was even significantly enhanced by IFN-γ. However, the production of IL-10 was strongly suppressed in cultures containing MSCs and IFN-γ. Preincubation of MSCs, but not of B cells, with IFN-γ induced the suppression of IL-10 secretion in cultures containing MSCs and B cells. The supernatants from IFN-γ-treated MSCs had no inhibitory effect, and the suppression of IL-10 production was abrogated if the MSCs and B cells were separated in a transwell system. Analysis of the gene expression of IFN-γ- or IFN-γ and LPS-treated MSCs revealed a strong upregulation of genes for indoleamine-2,3-dioxygenase (IDO), cyclooxygenase-2 (Cox-2) and programmed cell death-ligand 1 (PD-L1). While the inhibition of IDO activity or the inclusion of the neutralization monoclonal antibody anti-PD-L1 did not abrogate the suppression, indomethacin, an inhibitor of Cox-2, completely inhibited the MSC-mediated suppression of IL-10 production. Accordingly, the production of IL-10 by B cells was inhibited by exogenous prostaglandin E2. The results thus suggest that IFN-γ-treated MSCs strongly inhibit IL-10 production by activated B cells by a mechanism requiring cell contact and involving the Cox-2 pathway.

• MeSH
• aktivace lymfocytů účinky léků   MeSH
• antigeny CD274 antagonisté a inhibitory   genetika   imunologie   MeSH
• B-lymfocyty cytologie   účinky léků   imunologie   MeSH
• cyklooxygenasa 2 genetika   imunologie   MeSH
• difuzní komory kultivační MeSH
• dinoproston farmakologie   MeSH
• indolamin-2,3,-dioxygenasa genetika   imunologie   MeSH
• indomethacin farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• interferon gama farmakologie   MeSH
• interleukin-10 antagonisté a inhibitory   genetika   imunologie   MeSH
• kokultivační techniky MeSH
• kultivační média speciální farmakologie   MeSH
• lipopolysacharidy farmakologie   MeSH
• mezenchymální kmenové buňky cytologie   účinky léků   imunologie   MeSH
• mezibuněčná komunikace imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• neutralizující protilátky farmakologie   MeSH
• primární buněčná kultura MeSH
• regulace genové exprese MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• Guna-Flam, medicína nízkých dávek, fyziologická regulační medicína,
• MeSH
• cytokiny * farmakologie   terapeutické užití   MeSH
• interleukin-1 imunologie   MeSH
• interleukin-10 imunologie   MeSH
• komplementární terapie * MeSH
• lidé MeSH
• transformující růstový faktor beta imunologie   účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zánět * farmakoterapie   imunologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH

Mesenchymal stem cells (MSCs) represent a population of cells which have the ability to regulate reactivity of T and B lymphocytes by multiple mechanisms. The immunoregulatory activities of MSCs are strictly influenced by the cytokine environment. Here we show that two functionally distinct cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), significantly potentiate the ability of MSCs to inhibit IL-10 production by activated regulatory B cells (Bregs). However, MSCs in the presence of IL-4 or IFN-γ inhibit the IL-10 production by different mechanisms. Preincubation of MSCs with IFN-γ led to the suppression, but pretreatment with IL-4 of neither MSCs nor B cells resulted in the suppression of IL-10 production. The search for candidate regulatory molecules expressed in cytokine-treated MSCs revealed different patterns of the gene expression. Pretreatment of MSCs with IFN-γ, but not with IL-4, induced expression of indoleamine-2,3-dioxygenase, cyclooxygenase-2 and programmed cell death-ligand 1. To identify the molecule(s) responsible for the suppression of IL-10 production, we used specific inhibitors of the putative regulatory molecules. We found that indomethacine, an inhibitor of cyclooxygenase-2 (Cox-2) activity, completely abrogated the inhibition of IL-10 production in cultures containing MSCs and IFN-γ, but had no effect on the suppression in cell cultures containing MSCs and IL-4. The results show that MSCs can inhibit the response of B cells to one stimulus by different mechanisms in dependence on the cytokine environment and thus support the idea of the complexity of immunoregulatory action of MSCs.

• MeSH
• aktivace lymfocytů účinky léků   imunologie   MeSH
• antigeny CD279 genetika   imunologie   metabolismus   MeSH
• buněčné mikroprostředí účinky léků   imunologie   MeSH
• cyklooxygenasa 2 genetika   imunologie   metabolismus   MeSH
• cytokiny imunologie   metabolismus   farmakologie   MeSH
• ELISA MeSH
• exprese genu účinky léků   genetika   imunologie   MeSH
• indolamin-2,3,-dioxygenasa genetika   imunologie   metabolismus   MeSH
• interferon gama farmakologie   MeSH
• interleukin-10 imunologie   metabolismus   MeSH
• interleukin-4 farmakologie   MeSH
• interleukin-6 genetika   imunologie   metabolismus   MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• mezenchymální kmenové buňky účinky léků   imunologie   metabolismus   MeSH
• myši MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulační B-lymfocyty účinky léků   imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Coronary artery bypass grafting (CABG) is performed with the use of cardiopulmonary bypass (CPB) and cardioplegic arrest (CA) of the heart. The advantage of this technique, alternatively referred to as "on-pump" surgery, resides, for the surgeon, in relatively easy access to and manipulation with the non-beating, bloodless heart. However, the advantage that is, thereby, gained by the patient is paid off by an increased susceptibility to postoperative systemic inflammatory response syndrome (SIRS). Under unfavorable conditions, the inflammatory syndrome may develop into life-threatening forms of MODS (multiple organ dysfunction syndrome) or even MOFS (multiple organ failure syndrome). Deliberate avoidance of CPB, also known as "off-pump" surgery, attenuates early postoperative inflammation throughout its trajectory of SIRS→MODS→MOFS, but, in the long run, there appears to be no substantial difference in the overall mortality rates. In the last years, our knowledge of the pathophysiology of surgical inflammation has increased considerably. Recent findings, highlighting the as yet rather obscure role of pentraxin 3 (PTX3) in these processes, are discussed in this review article.

• MeSH
• antiflogistika imunologie   MeSH
• ateroskleróza imunologie   MeSH
• C-reaktivní protein genetika   imunologie   MeSH
• infarkt myokardu imunologie   MeSH
• interleukin-10 imunologie   MeSH
• kardiopulmonální bypass škodlivé účinky   metody   MeSH
• koronární bypass škodlivé účinky   metody   MeSH
• lidé MeSH
• sérový amyloidový protein genetika   imunologie   MeSH
• syndrom systémové zánětlivé reakce etiologie   genetika   imunologie   MeSH
• transkriptom MeSH
• vyvolaná zástava srdce škodlivé účinky   metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH