In pigs, the epitheliochorial placenta does not allow transfer of maternally derived antibodies or immune cells to the fetus. Thus, piglets are dependent on intake of colostrum for acquisition of passive immunity during the neonatal period. As well as immunoglobulin G (IgG), cellular components of colostrum, mainly lymphocytes, can enter the systemic circulation and secondary lymphoid organs of the neonate. In order to understand the function and immunological role of these cells, a flow cytometric study was undertaken to characterise the cellular profile and phenotype of T cells and NK cells present in porcine colostrum. The results indicated that the greatest numbers of lymphocytes were found on the first day of lactation. The predominant cell types in colostrum were CD8(+) single positive T cells (53.6%), followed by CD4(+)CD8(+) double positive T cells (21.1%), CD2(+)CD8(+) γδ T cells (15.0%) and NK cells (13.5%). CD4(+) single positive T cells (4.4%) and other γδ T cell subpopulations (1.8% CD2(-)CD8(-) and 0.4% CD2(+)CD8(-)) were present in colostrum at low levels. Although the profile of the T cell subpopulations during the first 3 days of lactation remained constant, the absolute numbers of T and NK cells decreased significantly in the first few hours of lactation. Expression of CCR7, CD11b, CD25, CD45RA and MHC class II was used to assess the activation status of T and NK cells in colostrum. T cell subpopulations expressed markers consistent with an effector memory phenotype, indicating that these were antigen-experienced cells. The phenotype of colostral T and NK cells suggests a role in mucosal immunity and potentially in transfer of passive immunity from sow to piglet.

• MeSH
• antigeny imunologie   MeSH
• buňky NK imunologie   MeSH
• fenotyp MeSH
• imunita získaná od matky * MeSH
• kolostrum imunologie   MeSH
• poporodní období imunologie   MeSH
• průtoková cytometrie veterinární   MeSH
• Sus scrofa imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Natural killer (NK) cells play a pivotal role in the immune response against viral infections, including SARS-CoV-2. However, our understanding of memory NK cell responses in the context of SARS-CoV-2 remains limited. To address this, we investigated the memory-like response of NK cells to SARS-CoV-2 peptides, presented by autologous cells. Blood samples from 45 donors underwent analysis for SARS-CoV-2 IgG antibodies, categorizing them into four groups based on the antibody kind and level. NK cells from SARS-CoV-2-experienced donors demonstrated enhanced degranulation and activation levels, IFNγ production and proliferative potential in response to SARS-CoV-2 peptides. Investigation of highly proliferating NK cells demonstrated the formation of distinct clusters depending on the SARS-CoV-2 peptide supplementation and the donor group. RNA sequencing revealed differential gene expression patterns, highlighting metabolism, protein transport, and immune response genes. Notably, KIR2DS4 expression correlated with enhanced IFNγ production, degranulation and proliferation levels, suggesting a role in SARS-CoV-2 recognition. Collectively, these findings provide detailed insights into antigen-specific NK cell responses to SARS-CoV-2 peptides, indicating potential mechanisms underlying NK cell activation in antiviral immunity.

• MeSH
• aktivace lymfocytů MeSH
• buňky NK * imunologie   MeSH
• COVID-19 * imunologie   MeSH
• degranulace buněk MeSH
• dospělí MeSH
• imunoglobulin G MeSH
• imunologická paměť MeSH
• interferon gama * imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protilátky virové krev   imunologie   MeSH
• receptory KIR genetika   metabolismus   MeSH
• SARS-CoV-2 * imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

SOT101 is a superagonist fusion protein of interleukin (IL)-15 and the IL-15 receptor α (IL-15Rα) sushi+ domain, representing a promising clinical candidate for the treatment of cancer. SOT101 among other immune cells specifically stimulates natural killer (NK) cells and memory CD8+ T cells with no significant expansion or activation of the regulatory T cell compartment. In this study, we showed that SOT101 induced expression of cytotoxic receptors NKp30, DNAM-1 and NKG2D on human NK cells. SOT101 stimulated dose-dependent proliferation and the relative expansion of both major subsets of human NK cells, CD56brightCD16- and CD56dimCD16+, and these displayed an enhanced cytotoxicity in vitro. Using human PBMCs and isolated NK cells, we showed that SOT101 added concomitantly or used for immune cell pre-stimulation potentiated clinically approved monoclonal antibodies Cetuximab, Daratumumab and Obinutuzumab in killing of tumor cells in vitro. The anti-tumor efficacy of SOT101 in combination with Daratumumab was assessed in a solid multiple myeloma xenograft in CB17 SCID mouse model testing several combination schedules of administration in the early and late therapeutic setting of established tumors in vivo. SOT101 and Daratumumab monotherapies decreased with various efficacy tumor growth in vivo in dependence on the advancement of the tumor development. The combination of both drugs showed the strongest anti-tumor efficacy. Specifically, the sequencing of both drugs did not matter in the early therapeutic setting where a complete tumor regression was observed in all animals. In the late therapeutic treatment of established tumors Daratumumab followed by SOT101 administration or a concomitant administration of both drugs showed a significant anti-tumor efficacy over the respective monotherapies. These results suggest that SOT101 might significantly augment the anti-tumor activity of therapeutic antibodies by increasing NK cell-mediated activity in patients. These results support the evaluation of SOT101 in combination with Daratumumab in clinical studies and present a rationale for an optimal clinical dosing schedule selection.

• MeSH
• buněčná cytotoxicita závislá na protilátkách MeSH
• buňky NK MeSH
• CD8-pozitivní T-lymfocyty patologie   MeSH
• cetuximab metabolismus   MeSH
• lektinové receptory NK-buněk - podrodina K * metabolismus   MeSH
• lidé MeSH
• mnohočetný myelom * patologie   MeSH
• monoklonální protilátky farmakologie   metabolismus   MeSH
• myši SCID MeSH
• myši MeSH
• receptor interleukinu-15 - alfa-podjednotka metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND/AIM: Melanoma is a skin cancer without effective therapy, showing high immunogenicity and mostly partial spontaneous regression (SR). The exact mechanisms of SR are still not well understood; therefore, the use of animal melanoma models is necessary to unravel the immunological processes during SR. MATERIALS AND METHODS: Skin melanoma samples (n=57) and peripheral blood samples (n=57) from the same animals were collected. Melanoma-bearing Libechov Minipigs (MeLiM) aged 3, 4, 6, 8, 10, 12, 20, and 32 weeks were used, and samples were analysed by flow cytometry for detection of immune cell subpopulations. RESULTS: The proportion of CD3-CD8+ (NK) cells in melanoma samples was found to be higher compared to blood samples at 6-8 weeks of age and then at 12 weeks of age. The population of CD4+CD8+ (effector/memory T helper) cells and CD4-CD8+ (cytotoxic T and NK) cells was also increased in melanoma compared to blood samples in 10-32-week-old pigs. The proportion of CD4-CD8+ cells in melanoma samples, then augmented until the 32nd week. On the contrary, the proportion of CD4+CD8- (naive T helper) cells was lower in melanoma samples versus blood samples in 6-32-week-old animals. CONCLUSION: Cytotoxic T cells were the most abundant population of tumour infiltrating immune cells found in MeLiM melanomas of animals aged 10-32 weeks, probably causing the destruction of melanoma cells. Furthermore, the development of specific (adaptive) immune response represented mainly by cytotoxic T cells seems to be crucial for the successful SR of porcine melanoma.

• MeSH
• buňky NK patologie   MeSH
• cytotoxické T-lymfocyty patologie   MeSH
• melanom * patologie   MeSH
• miniaturní prasata MeSH
• nádory kůže * MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

A small proportion of chronic myeloid leukemia patients treated with interferon-α (IFN-α) monotherapy are able to discontinue the treatment without disease relapse although residual leukemia cells are present. Recently, we showed that these patients have increased amount of NK-cells and a distinct blood cytokine profile. We now aimed to study the function of NK- and T-cells in order to understand the role of the immune system in maintaining the treatment response after IFN-α discontinuation. The study included 13 patients: 5 patients were still treated with IFN-α monotherapy (IFN-ON, median treatment time 163 months) and 8 had stopped the treatment successfully (IFN-OFF, median time without therapy 42 months). Detailed immunophenotype and cytokine production of NK- and T-cells was analyzed with flow cytometry. In addition, the cytotoxicity of NK-cells was studied using K562 as target cells and both the degranulation and direct killing was measured. Compared to healthy controls, IFN-OFF patients had increased proportion of CD4(+) effector memory (CCR7(-)CD45RA(-); median 23% vs. healthy 16%, p = 0.009) and CD8(+) central memory T-cells (CCR7(+)CD45RA(-); median 26% vs. healthy 14%, p = 0.004). Further, upon stimulation the IFN-γ/TNF-α cytokine secretion by CD4(+) T-cells was significantly enhanced in IFN-OFF patients (median 13.7% vs. healthy 7.8%, p = 0.01), and CD4+ effector and central memory cells were the main cytokine producers. No similar increase was observed in IFN-ON group (6.5%). In addition, the proportion of NK-cells was significantly increased in IFN-OFF patients (median IFN-OFF 24%, healthy 13%, p = 0.04), but their direct killing of K562 cells was impaired. The cytotoxicity of NK-cells was also diminished in IFN-ON patients. To conclude, in addition to elevated NK-cell count, IFN-OFF patients have increased amount of memory T-cells, which are able to induce strong cytokine response upon stimulation. This activity may contribute to the maintenance of prolonged remission after successful IFN-α discontinuation.

• MeSH
• buňky K562 MeSH
• buňky NK imunologie   metabolismus   patologie   MeSH
• chronická myeloidní leukemie krev   farmakoterapie   imunologie   patologie   MeSH
• dospělí MeSH
• imunologická paměť účinky léků   MeSH
• imunologické faktory aplikace a dávkování   MeSH
• interferon alfa aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet CD4 lymfocytů MeSH
• Th1 buňky imunologie   metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

IL-2 is potent imunostimulatory molecule that plays a key role in T and NK cell activation and expansion. IL-2 is approved by the FDA to treat metastatic renal cancer and melanoma, but its extremely short half-life and serious toxicities are significant limitations of its use. It was reported that in vivo biological activity of IL-2 can be increased by association of IL-2 with anti-IL-2 mAb (S4B6). IL-2/S4B6 mAb immunocomplexes were described to be highly stimulatory for NK and memory CD8(+) T cells and intermediately also for regulatory T cells. IL-2/JES6-1 mAb immunocomplexes are stimulatory solely for regulatory T cells. In this study we show that although both mentioned IL-2 immunocomplexes are less potent than free IL-2 in vitro, they possess extremely high stimulatory activity to expand activated naive CD8(+) T cells in vivo. IL-2 immunocomplexes expand activated naive CD8(+) T cells several hundred-fold times after four doses and more than 1000-fold times after six doses (1.5 microg/dose of IL-2), whereas free IL-2 given at the same dosage shows negligible activity. IL-2/S4B6 mAb immunocomplexes also induce massive expansion of NK cells (40% of DX5(+)NK1.1(+) cells in spleen). Importantly, activated naive CD8(+) T cells expanded by IL-2 immunocomplexes form robust population of functional memory cells. We also demonstrate in two distinct tumor models that IL-2/S4B6 mAb immunocomplexes possess considerable antitumor activity. Finally, by using radioactively labeled IL-2, we provide for first time direct evidence that IL-2 immunocomplexes have much longer half-life in circulation than free IL-2, being approximately 3 h vs <15 min, respectively.

• MeSH
• buňky NK imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• imunokomplex terapeutické užití   MeSH
• imunoterapie MeSH
• interleukin-2 terapeutické užití   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory imunologie   terapie   MeSH
• poločas MeSH
• převzatá imunita MeSH
• rekombinantní proteiny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem 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

Imunitnú odpoveď delíme na prirodzenú a adaptívnu, i keď takéto striktné delenie je sporné, lebo jeden typ imunity ovplyvňuje druhý a naopak. Navyše existuje skupina buniek a imunitných mechanizmov, ktoré stoja niekde na rozhraní. B-lymfocyty a T-lymfocyty sú základnými predstaviteľmi adaptívnej imunity. Ani jedni z nich netvoria jednotnú populáciu. B-lymfocyty majú 3 subpopulácie (folikulové, B1 a marginálnej zóny). Pri T-lymfocytoch je situácia zložitejšia. Existujú 2 základné skupiny, tie s antigénovým receptorom α, β a tie s antigénovým receptorom γ, δ. T-lymfocyty αβ sú veľmi heterogénne; poznáme pomocné, cytotoxické a regulačné. Navyše pomocné T-lymfocyty sa delia na 7 subpopulácií. Okrem uvedených efektorových B-lymfocytov a T-lymfocytov, každá skupina má svoj náprotivok v podobe pamäťových buniek, pričom pamäťové T-lymfocyty sú 3 typov. Ďalšie skupiny lymfocytov označujeme ako nekonvenčné. Reprezentujú ich bunky NK, NKT a MAIT. Napokon v nedávnej dobe sa objavila skupina buniek, ktorá je práve na rozhraní medzi prirodzenou a adaptívnou imunitou. Ide o prirodzené lymfoidné bunky (Innate Lymphoid Cells - ILC). Tie tiež nie sú jednotné; v súčasnosti rozlišujeme 3 ich základné populácie: ILC1, ILC2 a ILC3. Navyše v rámci danej rodiny možno rozlíšiť ďalšie subpopulácie. Vymenovanie uvedených typov buniek poukazuje na komplexnosť a vzájomnú prepojenosť imunitných procesov v záujme udržania biologickej integrity jedinca.

Immune response is divided into natural and adaptive although such strict division is rather contentious as one type of immunity influences another one and vice-versa; moreover, there are cells and immune mechanisms, which stay somewhere in an interface. B and T lymphocytes represent principal cells of adaptive immunity. Not one of them form a uniform population. B cells comprise of three subpopulations (follicular, B1, marginal zone). Concerning T cells, the situation is more complicated. There are two basic populations, that expressing T cell receptors α, β and that expressing γ, δ receptors. T cells αβ are very heterogeneous; we can distinguish helper, cytotoxic and regulatory cells. Moreover, among T helper cell, are there seven subsets. Except the above-mentioned effector B and T cells, each group has its counterpart in the form of memory cells, wherein the memory T cell are of three types. The other group of lymphocytes represent so-called unconventional cells. NK, NKT a MAIT are their representatives; they are also heterogeneous. Ultimately, a novel group of cells appeared recently. It stays just on the interphase between natural and adaptive immunity. We know these cells under the name innate lymphoid cells (ILCs). They are also not uniform - three basic populations are well characterized: ILC1, ILC2, ILC3. Moreover, in the frame of each family, we can distinguish more subsets. Enumeration of said cell types indicates complexity and mutual interconnection of immune processes in order to maintain biological integrity of an individual.

• Klíčová slova
• ILC-buňky,
• MeSH
• B-lymfocyty * fyziologie   imunologie   MeSH
• buňky NK fyziologie   imunologie   MeSH
• lidé MeSH
• podskupiny lymfocytů fyziologie   imunologie   MeSH
• T-lymfocyty * fyziologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Multiple myeloma (MM) is a disease which remains incurable. One of the main reasons is a weakened immune system that allows MM cells to survive. Therefore, the current research is focused on the study of immune system imbalance in MM to find the most effective immunotherapy strategies. Aiming to identify the key points of immune failure in MM patients, we analysed peripheral lymphocytes subsets from MM patients (n = 57) at various stages of the disease course and healthy individuals (HI, n = 15) focusing on T, NK, iNKT, B cells and NK-cell cytokines. Our analysis revealed that MM patients exhibited immune alterations in all studied immune subsets. Compared to HI, MM patients had a significantly lower proportion of CD4 + T cells (19.55% vs. 40.85%; p < 0.001) and CD4 + iNKT cells (18.8% vs. 40%; p < 0.001), within B cells an increased proportion of CD21LCD38L subset (4.5% vs. 0.4%; p < 0.01) and decreased level of memory cells (unswitched 6.1% vs. 14.7%; p < 0.001 and switched 7.8% vs. 11.2%; NS), NK cells displaying signs of activation and exhaustion characterised by a more than 2-fold increase in SLAMF7 MFI (p < 0.001), decreased expression of NKG2D (MFI) and NKp46 (%) on CD16 + 56 + and CD16 + 56- subset respectively (p < 0.05), Effective immunotherapy needs to consider these immune defects and monitoring of the immune status of MM patients is essential to define better interventions in the future.

• MeSH
• B-lymfocyty imunologie   MeSH
• buňky NK imunologie   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * krev   imunologie   terapie   MeSH
• NKT buňky imunologie   MeSH
• podskupiny lymfocytů imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The innate immunity is frequently accepted as a first line of relatively primitive defense interfering with the pathogen invasion until the mechanisms of 'privileged' adaptive immunity with the production of antibodies and activation of cytotoxic lymphocytes 'steal the show'. Recent advancements on the molecular and cellular levels have shaken the traditional view of adaptive and innate immunity. The innate immune memory or 'trained immunity' based on metabolic changes and epigenetic reprogramming is a complementary process insuring adaptation of host defense to previous infections.Innate immune cells are able to recognize large number of pathogen- or danger- associated molecular patterns (PAMPs and DAMPs) to behave in a highly specific manner and regulate adaptive immune responses. Innate lymphoid cells (ILC1, ILC2, ILC3) and NK cells express transcription factors and cytokines related to subsets of T helper cells (Th1, Th2, Th17). On the other hand, T and B lymphocytes exhibit functional properties traditionally attributed to innate immunity such as phagocytosis or production of tissue remodeling growth factors. They are also able to benefit from the information provided by pattern recognition receptors (PRRs), e.g. γδT lymphocytes use T-cell receptor (TCR) in a manner close to PRR recognition. Innate B cells represent another example of limited combinational diversity usage participating in various innate responses. In the view of current knowledge, the traditional black and white classification of immune mechanisms as either innate or an adaptive needs to be adjusted and many shades of gray need to be included.

• MeSH
• adaptivní imunita * MeSH
• B-lymfocyty imunologie   MeSH
• buňky NK imunologie   MeSH
• cytokiny genetika   imunologie   MeSH
• lidé MeSH
• přirozená imunita * MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH