• Klíčová slova
• močové cesty, infekce močových cest, praktické lékařství,
• MeSH
• infekce močového ústrojí MeSH

• Konspekt
• Patologie. Klinická medicína

• MeSH
• homologní transplantace metody   škodlivé účinky   využití   MeSH
• imunotoxiny klasifikace   terapeutické užití   MeSH
• reakce štěpu proti hostiteli účinky léků   účinky záření   MeSH
• T-lymfocyty imunologie   účinky léků   MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• Publikační typ
• přehledy MeSH

The expression of selected molecules was chosen to study porcine γδ lymphocytes and their CD2/CD8 subsets in different lymphoid organs in vivo and in vitro. Results indicate that many γδ T cells can constitutively express CD25 and MHC-II and that the frequency of γδ T cells positive for CD25, CD11b, SWC1 and SWC7 can be increased by stimulation. A diversified TCRδ repertoire was found inside CD25(+), CD11b(+), SWC1(-) and CD45RA(-) cells. Ontogenetic studies revealed various age and/or colonization dependency for expression of all studied molecules except of SWC7. Findings generally indicate that CD25 represent an activation molecule that probably marks a functionally distinct subsets, expression of CD11b is perhaps connected to early functions of naive γδ T cells in the periphery, SWC1 is lineage specific marker, SWC7 may represent an activation molecule with intrinsic or transient expression, and the expression of CD45RA/RC most likely defines naive and terminally differentiated cells.

• MeSH
• antigeny CD45 metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• prasata imunologie   MeSH
• receptor interleukinu-2 - alfa-podjednotka metabolismus   MeSH
• T-lymfocyty - podskupiny cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders. The percentage of CD2-, CD25+ and/or CD30+ MC was considerably lower in patients with indolent SM compared to patients with advanced SM, including aggressive SM and MC leukemia. Whereas CD25 and CD30 expression in MC could not be associated with prognosis, we found that lack of CD2 expression in MC is associated with a significantly reduced overall survival (OS) in patients with SM (p < 0.0001). Lack of CD2 was also associated with the presence of extramedullary involvement affecting the spleen, liver, and/or lymph nodes (odds ratio 2.63 compared to SM with CD2+ MC). Together, lack of CD2 expression in MC is a prognostic marker and indicator of reduced OS and extramedullary disease expansion in patients with SM.

• MeSH
• antigen Ki-1 * metabolismus   MeSH
• antigeny CD2 * metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastocyty * metabolismus   patologie   imunologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prognóza MeSH
• receptor interleukinu-2 - alfa-podjednotka * metabolismus   MeSH
• registrace * MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• systémová mastocytóza * metabolismus   patologie   mortalita   diagnóza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

Common variable immunodeficiency (CVID), the most frequent symptomatic immunoglobulin primary immunodeficiency, is associated with chronic T cell activation and reduced frequency of CD4(+) T cells. The underlying cause of immune activation in CVID is unknown. Microbial translocation indicated by elevated serum levels of lipopolysaccharide and soluble CD14 (sCD14) has been linked previously to systemic immune activation in human immunodeficiency virus/acquired immune deficiency syndrome (HIV-1/AIDS), alcoholic cirrhosis and other conditions. To address the mechanisms of chronic immune activation in CVID, we performed a detailed analysis of immune cell populations and serum levels of sCD14, soluble CD25 (sCD25), lipopolysaccharide and markers of liver function in 35 patients with CVID, 53 patients with selective immunoglobulin (Ig)A deficiency (IgAD) and 63 control healthy subjects. In CVID subjects, the concentration of serum sCD14 was increased significantly and correlated with the level of sCD25, C-reactive protein and the extent of T cell activation. Importantly, no increase in serum lipopolysaccharide concentration was observed in patients with CVID or IgAD. Collectively, the data presented suggest that chronic T cell activation in CVID is associated with elevated levels of sCD14 and sCD25, but not with systemic endotoxaemia, and suggest involvement of lipopolysaccharide-independent mechanisms of induction of sCD14 production.

• MeSH
• aktivace lymfocytů MeSH
• B-lymfocyty imunologie   MeSH
• běžná variabilní imunodeficience krev   imunologie   MeSH
• bronchiektazie krev   MeSH
• C-reaktivní protein imunologie   metabolismus   MeSH
• deficience IgA krev   imunologie   MeSH
• dospělí MeSH
• endotoxemie krev   imunologie   MeSH
• granulom krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipopolysacharidové receptory krev   imunologie   MeSH
• lipopolysacharidy krev   imunologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoci jater krev   MeSH
• receptor interleukinu-2 - alfa-podjednotka krev   imunologie   MeSH
• senioři MeSH
• splenomegalie krev   MeSH
• T-lymfocyty imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

T regulatory cells (Tregs) are essential for maintaining tolerance and preventing autoimmune diseases, such as type 1 diabetes (T1D). In our study, we investigated CD25 + FoxP3 + Tregs and thymic FoxP3 + Helios + Tregs in large cohorts of children with T1D at onset and with long-term T1D, and further in their relatives and healthy controls. We observed significantly decreased numbers of CD25 + FoxP3 + Tregs, but not FoxP3 + Helios + Tregs, in long-term patients compared with the control group and T1D onset. Furthermore, long-term T1D patients exhibited highly significant decrease of CD25 expression on both CD25 + FoxP3 + Tregs and FoxP3 + Helios + Tregs, independently on age or the duration of diabetes. A similar reduction of CD25 expression was also found in T1D relatives, more significant in those with positive autoantibodies. Low CD25 expression was associated with impaired signal transducer and activator of transcription 5 (STAT5) phosphorylation after IL-2 exposure. Our results show that the frequency of Tregs is altered in a large cohort of long-term T1D patients, a profound decrease in CD25 expression and altered IL-2 signaling are typical features of Tregs populations in long-term diabetic patients and their relatives.

• MeSH
• biologické markery MeSH
• buněčná diferenciace MeSH
• diabetes mellitus 1. typu diagnóza   etiologie   metabolismus   MeSH
• dítě MeSH
• forkhead transkripční faktory metabolismus   MeSH
• fosforylace MeSH
• imunofenotypizace MeSH
• interleukin-2 metabolismus   farmakologie   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• počet lymfocytů MeSH
• předškolní dítě MeSH
• receptor interleukinu-2 - alfa-podjednotka genetika   metabolismus   MeSH
• regulační T-lymfocyty cytologie   imunologie   metabolismus   MeSH
• signální transdukce MeSH
• studie případů a kontrol MeSH
• thymocyty cytologie   imunologie   metabolismus   MeSH
• transkripční faktor STAT5 MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) and CD1d-restricted invariant natural killer T (iNKT) cells are two cell types that are known to regulate immune reactions. Depletion or inactivation of Tregs using specific anti-CD25 antibodies in combination with immunostimulation is an attractive modality especially in anti-tumour immunotherapy. However, CD25 is not expressed exclusively on Tregs but also on subpopulations of activated lymphocytes. Therefore, the modulatory effects of the specific anti-CD25 antibodies can also be partially attributed to their interactions with the effector cells. Here, the effector functions of iNKT cells were analysed in combination with anti-CD25 mAb PC61. Upon PC61 administration, α-galactosylceramide (α-GalCer)-mediated activation of iNKT cells resulted in decreased IFN-γ but not IL-4 production. In order to determine whether mutual interactions between Tregs and iNKT cells take place, we compared IFNγ production after α-GalCer administration in anti-CD25-treated and "depletion of regulatory T cell" (DEREG) mice. Since no profound effects on IFNγ induction were observed in DEREG mice, deficient in FoxP3(+) Tregs, our results indicate that the anti-CD25 antibody acts directly on CD25(+) effector cells. In vivo experiments demonstrated that although both α-GalCer and PC61 administration inhibited TC-1 tumour growth in mice, no additive/synergic effects were observed when these substances were used in combination therapy.

• MeSH
• antigeny CD1d imunologie   metabolismus   MeSH
• ELISA MeSH
• experimentální nádory farmakoterapie   imunologie   patologie   MeSH
• exprese genu účinky léků   imunologie   MeSH
• forkhead transkripční faktory imunologie   metabolismus   MeSH
• galaktosylceramidy aplikace a dávkování   imunologie   farmakologie   MeSH
• interferon gama genetika   imunologie   metabolismus   MeSH
• interleukin-4 genetika   imunologie   metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• mezibuněčné signální peptidy a proteiny genetika   imunologie   metabolismus   MeSH
• monoklonální protilátky aplikace a dávkování   imunologie   farmakologie   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• NKT buňky účinky léků   imunologie   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• průtoková cytometrie MeSH
• receptor interleukinu-2 - alfa-podjednotka imunologie   metabolismus   MeSH
• regulační T-lymfocyty účinky léků   imunologie   metabolismus   MeSH
• tumor burden účinky léků   imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental HCC cells activated regulatory CD4+/CD25+/FoxP3+ T cells (Tregs). Conclusions: Loss of macroH2A1 in HCC cells drives cancer stem-cell propagation and evasion from immune surveillance.

• MeSH
• antigeny CD44 metabolismus   MeSH
• chemorezistence * MeSH
• forkhead transkripční faktory metabolismus   MeSH
• genový knockdown MeSH
• glykolýza MeSH
• hepatocelulární karcinom farmakoterapie   imunologie   metabolismus   patologie   MeSH
• histony metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolomika metody   MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky účinky léků   imunologie   patologie   MeSH
• nádorové mikroprostředí imunologie   MeSH
• nádory jater farmakoterapie   imunologie   metabolismus   patologie   MeSH
• parakrinní signalizace * MeSH
• receptor interleukinu-2 - alfa-podjednotka metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• regulační T-lymfocyty imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Abnormalities in CD4+CD25+ regulatory T cells (Treg) may contribute to type 1 diabetes (T1D) development. First-degree relatives of T1D patients are at increased risk especially when they carry certain HLA II haplotypes. Using two novel markers of CD4+CD25+ Treg (CD127- and FoxP3+ respectively), we evaluated number and function of Treg after specific stimulation with diabetogeneic autoantigens in 11 high-risk (according to HLA-linked risk) relatives of T1D patients and 14 age-matched healthy controls using a cytokine secretion assay based on interferon-gamma (IFN-gamma) production. High-risk relatives of T1D patients had significantly lower pre- and post-stimulatory number of CD127- Treg than that of healthy controls (P < 0.05). Labelling Treg with FoxP3+ demonstrated similar trend but did not reach statistical significance. Although the stimulation with diabetogenic autoantigens did not lead to a significant change in number of Treg in both groups, the defective function of Treg was performed by significantly higher activation of diabetogeneic T cells in high-risk relatives of T1D patients compared to healthy controls (P < or = 0.02). Individuals at increased HLA-associated genetic risk for T1D showed defects in Treg.

• MeSH
• antigeny CD4 analýza   MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• dospělí MeSH
• financování organizované MeSH
• forkhead transkripční faktory analýza   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mladiství MeSH
• počet lymfocytů MeSH
• průtoková cytometrie MeSH
• receptor interleukinu-2 - alfa-podjednotka analýza   MeSH
• receptor interleukinu-7 - alfa-podjednotka analýza   MeSH
• regulační T-lymfocyty imunologie   MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

MSCs produce CD4(+)CD25(+)FOX3(+) regulatory T (Treg) cells from activated peripheral blood mononuclear cells (PBMC), T-CD4+ and T-CD8+ cells in vitro and in vivo. Here we investigated whether the deficiency of androgen/AR in MSCs influence Treg induction from total PBMC, splenocytes, CD4+CD25-through AR/TGF-β interaction. Eight to 12-week-old wild type and general androgen receptor knockout (ARKO) mice were used. MSCs were collected, characterized and function of Treg cells was studied. Our result showed that depletion of AR suppressed the immunosuppressive effect of MSCs, and demonstrated that WT-MSC-induced Treg cell expansion was partially impaired by blocking androgen receptor signal. Furthermore, the levels of TGF-β were lower in the T cell coculture with ARKO-MSC compared to WT-MSC. Exposure of ARKO-MSC cells to exogenous active TGF-β partially restored the induction of Treg cell expansion by ARKO-MSC cells. Our data suggest that ARKO-MSC hampers Treg cell expansion and function via androgen/AR and TGF-β signal pathways interaction. To the best of our knowledge, this study is the first investigating the interaction of MSCs from ARKO mice and WT Tregs in an allogeneic co-culture model. Together, these results might provide great insight into treatment of inflammatory and autoimmune diseases.

• MeSH
• androgenní receptory MeSH
• autoimunitní nemoci * farmakoterapie   MeSH
• CD4-pozitivní T-lymfocyty MeSH
• CD8-pozitivní T-lymfocyty MeSH
• ELISA MeSH
• imunosupresivní léčba MeSH
• leukocyty mononukleární * MeSH
• lymfocytární deplece MeSH
• mezenchymální kmenové buňky * fyziologie   MeSH
• myši MeSH
• receptor interleukinu-2 - alfa-podjednotka MeSH
• regulační T-lymfocyty * fyziologie   MeSH
• transformující růstový faktor beta MeSH
• zánět * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• pozorovací studie MeSH
• práce podpořená grantem MeSH