The mammalian body possesses remarkable adaptability to cold exposure, involving intricate adjustments in cellular metabolism, ultimately leading to thermogenesis. However, cold-induced stress can impact immune response, primarily through noradrenaline-mediated pathways. In our study, we utilized a rat model subjected to short-term or long-term mild cold exposure to investigate systemic immune response during the cold acclimation. To provide human relevance, we included a group of regular cold swimmers in our study. Our research revealed complex relationship between cold exposure, neural signaling, immune response, and thermogenic regulation. One-day cold exposure triggered stress response, including cytokine production in white adipose tissue, subsequently activating brown adipose tissue, and inducing thermogenesis. We further studied systemic immune response, including the proportion of leukocytes and cytokines production. Interestingly, γδ T cells emerged as possible regulators in the broader systemic response, suggesting their possible contribution in the dynamic process of cold adaptation. We employed RNA-seq to gain further insights into the mechanisms by which γδ T cells participate in the response to cold. Additionally, we challenged rats exposed to cold with the Toll-like receptor 2 agonist, showing significant modulation of immune response. These findings significantly contribute to understanding of the physiological acclimation that occur in response to cold exposure.

• Klíčová slova
• Cold exposure, Cytokines, Immune response, TLR2, γδ T cells,
• MeSH
• aklimatizace imunologie   MeSH
• cytokiny metabolismus   MeSH
• hnědá tuková tkáň imunologie   metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• nízká teplota * MeSH
• receptory antigenů T-buněk gama-delta imunologie   metabolismus   MeSH
• T-lymfocyty imunologie   MeSH
• termogeneze imunologie   MeSH
• toll-like receptor 2 * metabolismus   genetika   imunologie   MeSH
• zánět * imunologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny MeSH
• receptory antigenů T-buněk gama-delta MeSH
• Tlr2 protein, rat MeSH Prohlížeč
• toll-like receptor 2 * MeSH

AIM: to investigate the dynamics of the T-cell immune response in rabbits with experimental autoimmune uveitis (EAU) of varying severity. MATERIALS AND METHODS: The experiment involved two groups of Chinchilla rabbits (15 rabbits in each group). The model of EAU was created. The clinical picture of intraocular inflammation of varying severity was assessed. The determination of the level of white blood cells (WBC), lymphocytes (Lymphs), CD3+, CD4+, CD8+, and CD16+ in the blood of rabbits was conducted. RESULTS: Group I - moderate and severe uveitis, Group II - uveitis of mild severity. WBC, Lymphs, CD3+, CD4+, CD16+ were elevated and statistically significant in both groups of animals compared to control parameters on all days of the experiment (3, 7, 10, 14, 21 days) (p.

• Klíčová slova
• T-cells response, autoimmune uveitis, experiment,
• MeSH
• autoimunitní nemoci * imunologie   krev   MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• T-lymfocyty imunologie   MeSH
• uveitida * imunologie   krev   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Psoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of surrogate lineage markers, respectively. Here, we used case-control settings, multiparameter flow cytometry, 5-OP-RU-loaded MR1-tetramers, Luminex technology and targeted qRT-PCR to dissect the cellular and transcriptional landscape of γδ and MR1-restricted blood T cells in untreated PV cases (n=21, 22 matched controls). High interpersonal differences in cell composition were observed, fueling transcriptional variability at healthy baseline. A minor subset of canonical CD4+CD8+MR1-tet+TCRVα7.2+ and CD4+CD8-MR1-tet+TCRVα7.2+ T cells was the most significantly underrepresented community in male PV individuals, whereas Vδ2+ γδ T cells expressing high levels of TCR and Vδ1-δ2- γδ T cells expressing intermediate levels of TCR were selectively enriched in affected males, partly reflecting disease severity. Our findings highlight a formerly unappreciated skewing of human circulating MAIT and γδ cytomes during PV, and reveal their compositional changes in relation to sex, CMV exposure, serum cytokine content, BMI, and inflammatory burden. Complementing numerical alterations, we finally show that flow-sorted, MAIT and γδ populations exhibit divergent transcriptional changes in mild type I psoriasis, consisting of differential bulk expression for signatures of cytotoxicity/type-1 immunity (EOMES, RUNX3, IL18R), type-3 immunity (RORC, CCR6), and T cell innateness (ZBTB16).

• Klíčová slova
• MR1, cytokines, gammadelta T lymphocytes, mucosal associated invariant T cells, psoriasis,
• MeSH
• buněčná diferenciace MeSH
• cytotoxicita imunologická MeSH
• dospělí MeSH
• krevní oběh MeSH
• lidé středního věku MeSH
• lidé MeSH
• MAIT buňky imunologie   MeSH
• MHC antigeny I. třídy metabolismus   MeSH
• mladý dospělý MeSH
• přirozená imunita MeSH
• protein promyelocytické leukemie s motivem zinkového prstu genetika   metabolismus   MeSH
• psoriáza imunologie   MeSH
• receptory antigenů T-buněk gama-delta metabolismus   MeSH
• T-lymfocyty imunologie   MeSH
• Th1 buňky imunologie   MeSH
• vedlejší histokompatibilní antigeny metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• MHC antigeny I. třídy MeSH
• MR1 protein, human MeSH Prohlížeč
• protein promyelocytické leukemie s motivem zinkového prstu MeSH
• receptory antigenů T-buněk gama-delta MeSH
• vedlejší histokompatibilní antigeny MeSH

Dendritic cells have been widely investigated in cancer immunotherapy clinical trials for the last two decades mainly due to their robust ability to elicit an adaptive anticancer immune response of the cellular and humoral types. Immature DCs can be easily loaded with desired antigens. However, to become efficient antigen-presenting cells, DCs must first undergo a process of maturation. Protocols for the generation of DCs for use in cancer immunotherapy, including the generation of a large number of immature DCs for antigen pulsing and the selection of a well-defined immunostimulatory agent to achieve complete and reproducible maturation, which is a crucial step for further stimulation of T cell activation, must carefully consider the characteristics of DC physiology. In this report, we provided a detailed protocol for DC generation, pulsation and activation with the subsequent induction of T cell-specific immune responses.

• Klíčová slova
• Anti-tumor immune response, Generation of dendritic cells, Phagocytosis, T cell activation,
• MeSH
• aktivace lymfocytů * MeSH
• apoptóza MeSH
• dendritické buňky imunologie   MeSH
• fagocytóza MeSH
• kultivované buňky MeSH
• lidé MeSH
• nádory imunologie   MeSH
• průtoková cytometrie metody   MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Bone marrow-derived mesenchymal stem cells (MSCs) modulate immune response and can produce significant levels of transforming growth factor-β (TGF-β) and interleukin-6 (IL-6). These 2 cytokines represent the key factors that reciprocally regulate the development and polarization of naive T-cells into regulatory T-cell (Treg) population or proinflammatory T helper 17 (Th17) cells. In the present study we demonstrate that MSCs and their products effectively regulate expression of transcription factors Foxp3 and RORγt and control the development of Tregs and Th17 cells in a population of alloantigen-activated mouse spleen cells or purified CD4(+)CD25(-) T-cells. The immunomodulatory effects of MSCs were more pronounced when these cells were stimulated to secrete TGF-β alone or TGF-β together with IL-6. Unstimulated MSCs produce TGF-β, but not IL-6, and the production of TGF-β can be further enhanced by the anti-inflammatory cytokines IL-10 or TGF-β. In the presence of proinflammatory cytokines, MSCs secrete significant levels of IL-6, in addition to a spontaneous production of TGF-β. MSCs producing TGF-β induced preferentially expression of Foxp3 and activation of Tregs, whereas MSC supernatants containing TGF-β together with IL-6 supported RORγt expression and development of Th17 cells. The effects of MSC supernatants were blocked by the inclusion of neutralization monoclonal antibody anti-TGF-β or anti-IL-6 into the culture system. The results showed that MSCs represent important players that reciprocally regulate the development and differentiation of uncommitted naive T-cells into anti-inflammatory Foxp3(+) Tregs or proinflammatory RORγt(+) Th17 cell population and thereby can modulate autoimmune, immunopathological, and transplantation reactions.

• MeSH
• buněčná diferenciace imunologie   MeSH
• buněčné kultury MeSH
• cytokiny biosyntéza   MeSH
• imunita MeSH
• kultivační média speciální farmakologie   MeSH
• mezenchymální kmenové buňky fyziologie   MeSH
• myši MeSH
• parakrinní signalizace imunologie   MeSH
• regulační T-lymfocyty imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• zánět imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• kultivační média speciální MeSH

Regulatory T cells (Tregs) are indispensable for maintaining self-tolerance by suppressing conventional T cells. On the other hand, Tregs promote tumor growth by inhibiting anticancer immunity. In this study, we identified that Tregs increase the quorum of self-reactive CD8+ T cells required for the induction of experimental autoimmune diabetes in mice. Their major suppression mechanism is limiting available IL-2, an essential T-cell cytokine. Specifically, Tregs inhibit the formation of a previously uncharacterized subset of antigen-stimulated KLRK1+ IL-7R+ (KILR) CD8+ effector T cells, which are distinct from conventional effector CD8+ T cells. KILR CD8+ T cells show superior cell-killing abilities in vivo. The administration of agonistic IL-2 immunocomplexes phenocopies the absence of Tregs, i.e., it induces KILR CD8+ T cells, promotes autoimmunity, and enhances antitumor responses in mice. Counterparts of KILR CD8+ T cells were found in the human blood, revealing them as a potential target for immunotherapy.

As well as protecting us from invading pathogens, like bacteria or viruses, our immune system can also identify dangerous cells of our own that may cause the body harm, such as cancer cells. Once detected, a population of immune cells called cytotoxic T cells launch into action to kill the potentially harmful cell. However, sometimes the immune system makes mistakes and attacks healthy cells which it misidentifies as being dangerous, leading to autoimmune diseases. Special immune cells called T regulatory lymphocytes, or ‘Tregs’, can suppress the activity of cytotoxic T cells, preventing them from hurting the body’s own cells. While this can have a positive impact and reduce the effects of autoimmunity, Tregs can also make the immune system less responsive to cancer cells and allow tumors to grow. But how Tregs alter the behavior of cytotoxic T cells during autoimmune diseases and cancer is poorly understood. While multiple mechanisms have been proposed, none of these have been tested in living animal models of these diseases. To address this, Tsyklauri et al. studied Tregs in laboratory mice which had been modified to have autoimmune diabetes, which is when the body attacks the cells responsible for producing insulin. The experiments revealed that Tregs take up a critical signaling molecule called IL-2 which cytotoxic T cells need to survive and multiply. As a result, there is less IL-2 molecules available in the environment, inhibiting the cytotoxic T cells’ activity. Furthermore, if Tregs are absent and there is an excess of IL-2, this causes cytotoxic T cells to transition into a previously unknown subset of T cells with superior killing abilities. Tsyklauri et al. were able to replicate these findings in two different groups of laboratory mice which had been modified to have cancer. This suggests that Tregs suppress the immune response to cancer cells and prevent autoimmunity using the same mechanism. In the future, this work could help researchers to develop therapies that alter the behavior of cytotoxic T cells and/or Tregs to either counteract autoimmune diseases, or help the body fight off cancer.

• Klíčová slova
• IL-2, T cells, autoimmunity, cytotoxic, immune suppression, immunology, inflammation, mouse, regulatory T cells,
• MeSH
• CD8-pozitivní T-lymfocyty MeSH
• diabetes mellitus 1. typu * patologie   MeSH
• imunologická tolerance MeSH
• interleukin-2 MeSH
• lektinové receptory NK-buněk - podrodina K MeSH
• lidé MeSH
• myši MeSH
• receptory interleukinu-7 MeSH
• regulační T-lymfocyty * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-2 MeSH
• KLRK1 protein, human MeSH Prohlížeč
• Klrk1 protein, mouse MeSH Prohlížeč
• lektinové receptory NK-buněk - podrodina K MeSH
• receptory interleukinu-7 MeSH

Adaptive immune responses are tailored to different types of pathogens through differentiation of naive CD4 T cells into functionally distinct subsets of effector T cells (T helper 1 (TH1), TH2, and TH17) defined by expression of the key transcription factors T-bet, GATA3, and RORγt, respectively. Regulatory T (Treg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated Treg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide Treg cells with enhanced suppressive capacity. Whether expression of these factors in Treg cells-as in effector T cells-is indicative of heterogeneity of functionally discrete and stable differentiation states, or conversely may be readily reversible, is unknown. Here we demonstrate that expression of the TH1-associated transcription factor T-bet in mouse Treg cells, induced at steady state and following infection, gradually becomes highly stable even under non-permissive conditions. Loss of function or elimination of T-bet-expressing Treg cells-but not of T-bet expression in Treg cells-resulted in severe TH1 autoimmunity. Conversely, following depletion of T-bet- Treg cells, the remaining T-bet+ cells specifically inhibited TH1 and CD8 T cell activation consistent with their co-localization with T-bet+ effector T cells. These results suggest that T-bet+ Treg cells have an essential immunosuppressive function and indicate that Treg cell functional heterogeneity is a critical feature of immunological tolerance.

• MeSH
• aktivace lymfocytů MeSH
• autoimunita imunologie   MeSH
• buňky Th17 cytologie   imunologie   MeSH
• CD8-pozitivní T-lymfocyty cytologie   imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• myši MeSH
• proteiny T-boxu metabolismus   MeSH
• regulační T-lymfocyty cytologie   imunologie   metabolismus   MeSH
• separace buněk MeSH
• Th1 buňky cytologie   imunologie   MeSH
• Th2 buňky cytologie   imunologie   MeSH
• transkripční faktor T-bet MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• proteiny T-boxu MeSH
• transkripční faktor T-bet MeSH

Regulatory T cells have emerged as an important mechanism of regulating tolerance and T cell responses. CD4+ regulatory T cells can be divided into two main groups, natural regulatory T cells, which express high levels of CD25 on their cell surface and phenotypically diverse adaptive (antigen induced) regulatory T cells. Natural regulatory T cells are made in the thymus, and require strong costimulatory signals for induction and maintenance, express a transcription factor called Foxp3, and function by a largely unknown mechanism. Adaptive (antigen induced) regulatory T cells are made by sub-optimal antigenic signals in the periphery, in the presence of immunosuppressive cytokines, often in special circumstances, such as chronic viral infections or after mucosal administration of antigen, and rely on cytokines such as IL-10 and TGF-beta for suppression. Regulatory T cells offer a great potential for the treatment of autoimmune diseases and during transplantation.

• MeSH
• autoimunita imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• lidé MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

It is well established that lymphopenia induces the formation of the memory-phenotype T cells without the exposure to foreign antigens. More recently, the memory-phenotype antigen-inexperienced memory T cells were described in lymphoreplete mice and called virtual memory T cells. In this review, we compare multiple aspects of the biology of lymphopenia-induced memory T cells and virtual memory T cells, including cytokine requirements, the role of T-cell receptor specificity in the differentiation process, gene expression signature, and the immune response. Based on this comparison, we conclude that lymphopenia-induced memory T cells and virtual memory T cells most likely represent a single T-cell subset, for which we propose a term 'homeostatic memory T cells'.

• Klíčová slova
• Drc1/Ccdc164, Homeostatic memory, Lymphopenia, T cell, TCR, Virtual memory,
• MeSH
• buněčná diferenciace imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   patologie   MeSH
• cytokiny imunologie   MeSH
• imunologická paměť * MeSH
• lidé MeSH
• lymfopenie imunologie   patologie   MeSH
• modely imunologické * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH

Allogeneic cancer cell lines serve as universal source of tumor-associated antigens in cancer vaccines. Immunogenic high hydrostatic pressure-killed cancer cells derived from cell lines can be used for the generation of dendritic cell (DC)-based active cellular immunotherapy of non-small cell lung cancer (NSCLC). We investigated the expression of 12 known NSCLC tumor-associated antigens (TAA) (CEA, MAGE-A1, MAGE-A3, MAGE-A4, PRAME, hTERT, HER2, MUC1, Survivin, STEAP1, SOX2 and NY-ESO-1) in 6 NSCLC cell lines as candidates for the generation of DC-based lung cancer vaccine. We showed that the selected antigenic profile of these cell lines overlaps to various degrees with that of primary NSCLC tumors (n = 52), indicating that 4 out of 6 NSCLC cell lines would be suitable for DC-based vaccine generation. We further investigated the presence of TAA-specific T cells in blood of NSCLC patients (n = 32) using commercially available peptide mixes in an in vitro stimulation assay. IFN-γ+CD8+ and IFN-γ+CD4+ T cell responses to all antigens were detected in NSCLC patients. Interestingly, despite higher TAA expression in squamous cell carcinoma (SCC) the responsiveness of patients' T cells to stimulation was significantly lower in SCC patients than in adenocarcinoma (AC) patients. This suggests qualitative differences in T cell functionality between NSCLC subtypes. Based on this study, and in order to maximize the amount of treatable patients, we selected a mix of H520 and H522 NSCLC cell lines for DC-based vaccine preparation. We also established a minimal panel of antigenic peptide mixes (CEA, hTERT, PRAME, HER2) for immunomonitoring of T cell responses during the DC-based lung cancer immunotherapy in Phase I lung cancer clinical trial (NCT02470468).

• Klíčová slova
• Cancer cell lines, Dendritic cell-based immunotherapy, Immunomonitoring, Non-small cell lung cancer, T cells, Tumor antigens,
• MeSH
• antigenní specifita receptorů T-buněk * MeSH
• antigeny nádorové imunologie   MeSH
• cytotoxické T-lymfocyty imunologie   metabolismus   MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• imunoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory plic imunologie   metabolismus   patologie   terapie   MeSH
• nemalobuněčný karcinom plic imunologie   metabolismus   patologie   terapie   MeSH
• protinádorové vakcíny MeSH
• senioři MeSH
• staging nádorů MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny nádorové MeSH
• protinádorové vakcíny MeSH