Mucosal-associated invariant T-cells (MAIT) are unconventional T-cells with cytotoxic and pro-inflammatory properties. Previous research has reported contradictory findings on their role in cancerogenesis with data being even scarcer in haematological malignancies. Here, we report the results of a systematic analysis of MAIT cells in treatment-naïve patients with a broad range of haematological malignancies. We analysed peripheral blood of 204 patients and 50 healthy subjects. The pool of haematological patients had a statistically significant lower both the absolute value (median values, 0.01 × 109/L vs. 0.05 × 109/L) of MAIT cells and their percentage (median values 0.94% vs. 2.56%) among T-cells compared to the control group. Separate analysis showed that the decrease in the absolute number of MAIT cells is significant in patients with acute myeloid leukaemia, myeloproliferative neoplasms, plasma cell myeloma, B-cell non-Hodgkin lymphomas, otherwise not specified, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma compared to the control population. Furthermore, in haematological malignancies, MAIT cells overexpress PD-1 (average values, 51.7% vs. 6.7%), HLA-DR (average values, 40.2% vs. 7%), CD38 (average values, 25.9% vs. 4.9%) and CD69 (average values, 40.2% vs. 9.2%). Similar results were obtained when comparing patients with individual malignancies to the control population. Our data show that the depletion of circulating MAIT cells is a common observation in a broad spectrum of haematological malignancies. In addition to their reduced numbers, MAIT cells acquire an activated/exhausted phenotype.
- MeSH
- antigeny CD279 * imunologie metabolismus MeSH
- antigeny CD38 metabolismus imunologie MeSH
- CD antigeny metabolismus MeSH
- diferenciační antigeny T-lymfocytů metabolismus MeSH
- dospělí MeSH
- hematologické nádory * imunologie MeSH
- imunofenotypizace MeSH
- lektiny typu C MeSH
- lidé středního věku MeSH
- lidé MeSH
- MAIT buňky * imunologie MeSH
- membránové glykoproteiny imunologie MeSH
- mladý dospělý MeSH
- počet lymfocytů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Around half of people with severe COVID-19 requiring intensive care unit (ICU) treatment will survive, but it is unclear how the immune response to SARS-CoV-2 differs between ICU patients that recover and those that do not. We conducted whole-blood immunophenotyping of COVID-19 patients upon admission to ICU and during their treatment and uncovered marked differences in their circulating immune cell subsets. At admission, patients who later succumbed to COVID-19 had significantly lower frequencies of all memory CD8+ T cell subsets, resulting in increased CD4-to-CD8 T cell and neutrophil-to-CD8 T cell ratios. ROC and Kaplan-Meier analyses demonstrated that both CD4-to-CD8 and neutrophil-to-CD8 ratios at admission were strong predictors of in-ICU mortality. Therefore, we propose the use of the CD4-to-CD8 T cell ratio as a marker for the early identification of those individuals likely to require enhanced monitoring and/or pro-active intervention in ICU.
- MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- COVID-19 imunologie MeSH
- imunofenotypizace metody MeSH
- jednotky intenzivní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet lymfocytů metody MeSH
- poměr CD4 a CD8 lymfocytů metody MeSH
- prospektivní studie MeSH
- SARS-CoV-2 imunologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Coronavirus infections are frequent viral infections in several species. As soon as the severe acute respiratory syndrome (SARS) appeared in the early 2000s, most of the research focused on pulmonary disease. However, disorders in immune response and organ dysfunctions have been documented. Elderly individuals with comorbidities exhibit worse outcomes in all the coronavirus that cause SARS. Disease severity in SARS-CoV-2 infection is related to severe inflammation and tissue injury, and effective immune response against the virus is still under analysis. ACE2 receptor expression and polymorphism, age, gender and immune genetics are factors that also play an essential role in patients' clinical features and immune responses and have been partially discussed. The present report aims to review the physiopathology of SARS-CoV-2 infection and propose new research topics to understand the complex mechanisms of viral infection and viral clearance.
- MeSH
- angiotensin-konvertující enzym 2 genetika metabolismus MeSH
- biologické markery MeSH
- COVID-19 komplikace imunologie metabolismus virologie MeSH
- cytokiny metabolismus MeSH
- energetický metabolismus MeSH
- interakce hostitele a patogenu imunologie MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- náchylnost k nemoci imunologie MeSH
- podskupiny lymfocytů imunologie metabolismus MeSH
- přirozená imunita MeSH
- receptor angiotensinu typ 2 metabolismus MeSH
- replikace viru MeSH
- SARS-CoV-2 fyziologie MeSH
- syndrom uvolnění cytokinů etiologie metabolismus MeSH
- virové receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Vaccination constitutes one of the major breakthroughs in human medicine. At the same time, development of more immunogenic vaccine alternatives to using aluminium-based adjuvants is one of the most important phases of vaccination development. Among different sources of carbohydrate polymers, including plants, microbes and synthetic sources tested, glucans were found to be the most promising vaccine adjuvant, as they alone stimulate various immune reactions including antibody production without any negative side effects. The use of glucan particles as a delivery system is a viable option based on the documented efficient antigen loading and receptor-targeted uptake in antigen-presenting cells. In addition to particles, soluble glucans can be used as novel hydrogels or as direct immunocyte-targeting delivery systems employing novel complexes with oligodeoxynucleotides. This review focuses on recent advances in glucan-based vaccine development from glucan-based conjugates to a glucan-based delivery and adjuvant platform.
- MeSH
- adjuvancia imunologická * MeSH
- beta-glukany imunologie terapeutické užití MeSH
- hydrogely terapeutické užití MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- oligodeoxyribonukleotidy MeSH
- prezentace antigenu MeSH
- vakcinace MeSH
- vakcíny imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Mannose-binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro-organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non-pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n = 33), and three groups of patients with a history of pregnancy complications, including preterm labour (n = 29), recurrent miscarriage (n = 19) or unexplained intrauterine foetal death (IUFD; n = 17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341 ng/mL; activity 100% (IQR: 62%-100%)), compared to women with the history of IUFD (684 ng/mL, P = .008; activity 8.5% (IQR: 0%-97.8%), P = .011), recurrent miscarriage (524 ng/mL, P = .022; activity 44% (IQR: 4%-83%), P = .011) or preterm labour (799 ng/mL, P = .022; activity 62.5% (IQR: 0%-83%), P = .003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.
- MeSH
- dospělí MeSH
- komplikace těhotenství krev epidemiologie MeSH
- lektin vázající mannosu krev MeSH
- lektinová dráha komplementu imunologie MeSH
- lidé MeSH
- přirozená imunita imunologie MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- těhotenství MeSH
- výsledek těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.
- MeSH
- lidé MeSH
- tropická malárie epidemiologie imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- subsaharská Afrika MeSH
We aimed to evaluate in vivo effects of abatacept on phenotypes of T and B cells in the circulation of myositis patients in a sub-study of the ARTEMIS trial. Twelve patients with paired frozen PBMCs before and after 6-month abatacept treatment were included in this sub-study where mass cytometry (CyTOF) was chosen as a technology to be tested for its utility in a real-life clinical immune monitoring setting. Using CyTOF, the peripheral T cell phenotypes demonstrated considerable variation over time and between individuals precluding the identification of treatment-specific changes. We therefore conclude that studies of patient cohorts displaying wide clinical heterogeneity using mass cytometry must be relatively large in order to be suited for discovery research and immune monitoring. Still, we did find some correlations with functional muscle outcome, namely positive correlations between the ratio of CD4+ T cells and CD8+ T cells (CD4/CD8) in peripheral blood samples both at baseline and after treatment with muscle endurance improvement as assessed by the functional index-2 (FI-2) test. Our data suggest that the CD4/CD8 ratio in circulation at time of active disease may be a predictor of treatment efficacy in myositis patients.
- MeSH
- abatacept terapeutické užití MeSH
- dermatomyozitida krev farmakoterapie imunologie MeSH
- dospělí MeSH
- imunosupresiva terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- podskupiny B-lymfocytů účinky léků MeSH
- polymyozitida krev farmakoterapie imunologie MeSH
- T-lymfocyty - podskupiny účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Regulatory T cells (Tregs) play a critical role in the maintenance of a pregnancy. While the kinetics of the number of peripheral blood Tregs has been satisfactorily described in mouse models, analysis of these cell populations in human pregnancy is complicated by high variability in the quantity of Tregs and inconsistencies in the markers used for detecting different types of Treg. In the light of this, we set out to investigate the kinetics of various types of Treg, including CD45RA, GARP and PD-1(+) Tregs, in the peripheral blood of pregnant women in the first, second and third trimester, and at the time of delivery. Tregs, defined as a CD4(+)CD25(++)CD127(dim)Foxp3(+) population of leucocytes, were detected using flow cytometry. Natural thymus-derived Tregs and induced Tregs in the peripheral blood were distinguished by the expression or absence of a Helios marker, respectively. Our results showed that during normal pregnancy the sizes of various Treg subpopulations varied across women and also in an individual woman did not remain constant but varied significantly, most notable being the decrease observed at the time of delivery. Helios(-) cells were significantly less frequent in the peripheral blood of healthy pregnant women than Helios(+) cells, and the majority of Tregs were Helios(+)PD-1(+) Tregs.
- MeSH
- buněčná diferenciace MeSH
- forkhead transkripční faktory metabolismus MeSH
- imunofenotypizace MeSH
- kultivované buňky MeSH
- lidé MeSH
- počet lymfocytů MeSH
- průtoková cytometrie MeSH
- regulační T-lymfocyty imunologie MeSH
- T-lymfocyty - podskupiny imunologie MeSH
- těhotenství imunologie MeSH
- thymus imunologie MeSH
- transformující růstový faktor beta krev MeSH
- transkripční faktor Ikaros metabolismus MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé MeSH
- těhotenství imunologie MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Chronic inflammation has been implicated as the underlying mechanism responsible for the pathophysiology of preterm labour. Mannose-binding lectin (MBL) plays a central role in the innate immune response and is thus an important component of the first line of defense. The aim of this study was to investigate whether serum concentrations of MBL correlated with the incidence of preterm birth and low birthweight in a cohort of women with signs of threatened preterm birth. A cohort of 60 patients who presented with regular contractions and/or short cervix (group A) between 24 and 32 weeks of gestation and 20 healthy controls (group B) who had no pregnancy complications and delivered at term were recruited into a prospective study. The following outcomes were recorded: presence of preterm labour and birthweight in all patients. MBL and high sensitivity C-reactive protein levels were measured in all serum samples. The serum concentrations of MBL were significantly reduced in patients with threatened preterm labour (Group A), compared to the control Group B. Furthermore, infants born to Group A mothers with MBL deficiency (n = 13, MBL ≤100 ng/mL) had significantly lower birthweights, compared to those born to Group A women with normal MBL serum concentrations (P < .0001). Our small cohort study demonstrated a strong association between MBL deficiency and preterm delivery, and associated low birthweight. MBL deficiency could thus be considered an important risk factor for preterm birth.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- kohortové studie MeSH
- lektin vázající mannosu krev nedostatek MeSH
- lidé MeSH
- porodní hmotnost MeSH
- předčasná porodní činnost krev MeSH
- předčasný porod krev MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- těhotenství MeSH
- vrozené poruchy metabolismu komplikace epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Mucosal-associated invariant T (MAIT) cells contain two main subpopulations, CD8(+) and double-negative (DN) cells. The first reports suggested that subpopulations of MAIT cells have similar phenotype and function. Recent works, however, demonstrate that the subpopulations have different ontogenesis and are differentially affected by xenobiotic treatment. In this work, we re-examined the possible differences between subpopulations of MAIT cells. We demonstrate that the main subpopulations of MAIT cells (CD8 and DN) are relatively uniform in terms of both phenotype and function. Both populations are memory/activated, tissue-homing and pro-inflammatory. CD8(+) MAIT cells are better equipped for pro-inflammatory functions as they express higher levels of CD16 and NKG2D, produce more pro-inflammatory cytokines (TNF-α and IFN-γ) and have higher cytotoxic potential (contain more granzyme B and express higher levels of CD107A upon stimulation). Our study contributes to the understanding of the heterogeneity of MAIT cell population.
- MeSH
- biologické markery metabolismus MeSH
- buněčný rodokmen imunologie MeSH
- CD8-pozitivní T-lymfocyty cytologie imunologie MeSH
- dospělí MeSH
- exprese genu MeSH
- GPI-vázané proteiny genetika imunologie MeSH
- granzymy genetika imunologie MeSH
- imunofenotypizace MeSH
- imunologická paměť * MeSH
- interferon gama genetika imunologie MeSH
- lektinové receptory NK-buněk - podrodina K genetika imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- MAIT buňky cytologie imunologie MeSH
- membránový protein 1 asociovaný s lyzozomy genetika imunologie MeSH
- receptory IgG genetika imunologie MeSH
- TNF-alfa genetika imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH