The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαβ+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease.

• MeSH
• aktivace lymfocytů imunologie   MeSH
• antigeny CD38 imunologie   MeSH
• antigeny CD45 metabolismus   MeSH
• antigeny CD95 imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfoproliferativní nemoci imunologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• signální transdukce imunologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD38 MeSH
• antigeny CD45 MeSH
• antigeny CD95 MeSH

PURPOSE: Esophageal cancer (EC) is one of the most lethal gastrointestinal malignancies. Immunotherapy is a promising treatment modality for this disease. However, broader implementation of EC immunotherapy has been discouraged because of insufficient understanding of tumor interactions with the immune system. As with other malignancies, the current research on EC focuses on deciphering the immune cell signatures within the tumor microenvironment. However, the disease-elicited immune cell profiles in the paratumoral compartments are largely unknown. METHODS: We examined the immune cell signatures in 62 tissue samples from 16 EC patients in different esophageal tissue compartments: tumor tissue, peritumoral tissue, healthy esophageal tissue, and adjacent lymph nodes. We analyzed the proportions and distribution patterns of NK cells and CD4+ and CD8+ T cells as well as their death receptor (FasR, FasR/DR3)-expressing subpopulations. The analyzed data were then compared and correlated with the patients' clinicopathological data. RESULTS: We found that the FasR+ NK cells, CD4+ and CD8+ T cells infiltrated lymph nodes at the lowest levels and that the FasR+DR3+ CD4+ T cells were enhanced in tumors. The comparisons with the clinicopathological data revealed a major impact of active smoking on the reduction in paratumoral NK cells and the upregulation of FasR in tumor-infiltrating NK and CD8+ T cells. The lymph node metastatic stage, tumor stage, and Mandard grade correlated with the compartmental proportions of the evaluated immune cells. CONCLUSION: The novel association of the disease state with tumoral and paratumoral immune cell signatures suggests new possibilities for personalized immunotherapy for EC patients.

• Klíčová slova
• Death receptor 3, Esophageal cancer, Fas receptor, Mandard tumor regression grade, Peritumoral lymphocytes, Tumor-infiltrating lymphocytes,
• MeSH
• adenokarcinom imunologie   patologie   terapie   MeSH
• antigeny CD95 imunologie   MeSH
• buňky NK imunologie   patologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   patologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   patologie   MeSH
• imunoterapie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické uzliny imunologie   patologie   MeSH
• lymfocyty imunologie   patologie   MeSH
• nádory jícnu imunologie   patologie   terapie   MeSH
• senioři MeSH
• skvamózní karcinom jícnu imunologie   patologie   terapie   MeSH
• studie případů a kontrol MeSH
• T-lymfocyty - podskupiny imunologie   patologie   MeSH
• tumor infiltrující lymfocyty imunologie   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD95 MeSH

INTRODUCTION: Cardiac surgery directly initiates a systemic inflammatory response with the activation of both cellular and humoral parts of the immune system. Exaggerated immune system activation is associated with a risk of life-threatening multi-organ dysfunction (MOD) and increased morbidity and mortality in the postoperative period. The immune system response is regulated and terminated by inhibitory mechanisms, including the regulatory membrane molecules, such as CD200R, CD95, CD95L and soluble sCD200R. METHODS: We measured the expression of CD95, CD95L, CD200R and sCD200R molecules in granulocyte and monocyte populations in blood samples of 30 patients who underwent coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). Samples collected before surgery, after surgery and in the postoperative period were analyzed by flow cytometry and ELISA. RESULTS: We found a significant increase in the percentage of granulocytes featuring the anti-inflammatory molecule CD200R (from 5% to 17.8%) after surgery. We presume that these cells were less susceptible to apoptosis because they rarely expressed CD95 as the CD200R(+)CD95(-) granulocyte sub-population prevailed. Only a small percentage of CD200R(+) granulocytes expressed simultaneously CD95 (from 0.5 to 2.06 %). This small population of CD200R(+)CD95(+) cells decreased expression of CD200R after surgery and, thus, was likely to be a source of increased sCD200R in serum (from 96 to 294 ng/mL). Also, the expression of CD95L on CD200R(+) granulocytes and CD95 on CD200R(+) monocytes was affected by surgery. The percentage of CD200R(+) monocytes was elevated on the 1(st) postoperative day (from 30.6 to 49.4 %) and dropped below the preoperative value on the 7(th) day after surgery (from 30.6 to 19.8 %). This population comprised mainly CD200R(+)CD95(+) monocytes in which the enhanced expression of CD95 was found. CONCLUSION: Our data show that the expression of CD200R, CD95 and CD95L was influenced by cardiac surgery and imply the role of these membrane molecules in cell regulation-inhibition and apoptosis following cardiac surgery.

• Klíčová slova
• CD200R, CD95, CD95L, CPB, SIRS, apoptosis, cardiac surgery, regulatory molecules, sCD200R,
• MeSH
• antigeny CD95 krev   imunologie   MeSH
• antigeny povrchové krev   imunologie   MeSH
• apoptóza imunologie   MeSH
• elektivní chirurgické výkony MeSH
• granulocyty imunologie   metabolismus   MeSH
• koronární bypass * MeSH
• lidé MeSH
• ligand Fas krev   imunologie   MeSH
• monocyty imunologie   metabolismus   MeSH
• orexinové receptory MeSH
• přirozená imunita * MeSH
• receptory buněčného povrchu krev   imunologie   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD95 MeSH
• antigeny povrchové MeSH
• CD200R1 protein, human MeSH Prohlížeč
• FAS protein, human MeSH Prohlížeč
• ligand Fas MeSH
• orexinové receptory MeSH
• receptory buněčného povrchu MeSH

In the recent past, it has repeatedly been reported that CD4 cells play an important role in the immunology of chronic myeloid leukaemia. It was therefore of interest to test their activity in an animal model using bcr-abl-transformed cells. BALB/c mice were four times immunized with a DNA vaccine carrying the bcr-abl fusion gene. Two weeks after the last vaccine dose, the animals were challenged with syngeneic bcr-abl-transformed 12B1 cells which form solid tumors after subcutaneous administration. At the time of challenge, animals were treated with antibodies against the CD8+ T cells or CD4+ T cells. The efficacy of the depletion was monitored and found highly effective. All nonimmunized animals developed tumors. All animals untreated with the antibodies as well as those in which CD8+ T cells had been depleted, were fully protected against the challenge. On the other hand, almost all mice treated with anti-CD4+ antibody developed tumors. These results strongly suggested that the CD4+ T cells acted as effectors in the present system.

• MeSH
• antigeny CD95 imunologie   metabolismus   MeSH
• bcr-abl fúzové proteiny genetika   imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• CD8-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• DNA vakcíny imunologie   MeSH
• histokompatibilita - antigeny třídy II imunologie   metabolismus   MeSH
• imunizace MeSH
• lidé MeSH
• ligand Fas metabolismus   MeSH
• lymfocytární deplece MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nádorová transformace buněk genetika   imunologie   MeSH
• nádory genetika   imunologie   mortalita   prevence a kontrola   MeSH
• protinádorové vakcíny genetika   imunologie   MeSH
• slezina cytologie   imunologie   MeSH
• transformované buněčné linie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD95 MeSH
• bcr-abl fúzové proteiny MeSH
• DNA vakcíny MeSH
• histokompatibilita - antigeny třídy II MeSH
• ligand Fas MeSH
• protinádorové vakcíny MeSH

Many viruses are known to disarm or suppress the cell death machinery of infected cells. Apoptotic cell death can be activated by aggregation of the CD95 cell surface death receptor in sensitive cells, and in most insensitive cells treated with sensitizing agents such as interferon-gamma or inhibitors of protein synthesis. We show that, subsequent to sequestration and inactivation of the p53 tumour suppressor protein, SV40 abrogates p53-dependent, DNA damage-inducible up-regulation of CD95 surface expression. Loss of surface up-regulation of CD95 after sub-lethal mitomycin C treatment resulted in an impaired enhancement of both caspase-8 cleavage and apoptotic cell death following CD95 aggregation. We conclude that infection of human cells with SV40 virus strongly inhibits DNA damage-induced enhancement of CD95-mediated apoptosis.

• MeSH
• adenokarcinom MeSH
• antigeny CD95 genetika   imunologie   MeSH
• apoptóza MeSH
• buněčný cyklus genetika   MeSH
• imunoglobulin G MeSH
• lidé MeSH
• monoklonální protilátky MeSH
• nádorové buňky kultivované MeSH
• nádory prsu MeSH
• opičí virus SV40 fyziologie   MeSH
• poškození DNA * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD95 MeSH
• imunoglobulin G MeSH
• monoklonální protilátky MeSH