Mediated Immunity In Patients Research Articles

Elevated Nucleoprotein-Induced Interferon-γ Release in COVID-19 Patients Detected in a SARS-CoV-2 Enzyme-Linked Immunosorbent Spot Assay

Background: A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Data on SARS-CoV-2 specific T-cell responses is scarce, but various studies suggest a suppressed T-cell mediated immunity in patients with COVID-19. Methods: The objective of the present study was to determine functional T-cell responses to SARS-CoV-2 antigens (mosaic surface protein and nucleoprotein), by using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay, in patients with RT-PCR confirmed COVID-19. T-cell immune responses were evaluated in patients with severe disease admitted to the intensive care unit (ICU), patients with moderate disease treated on the pulmonary ward and healthy volunteers. Findings: More than half of the 19 COVID-19 patients sampled at ≥14 days after the onset of symptoms showed a significant T-cell response against the nucleoprotein. A subgroup of nine (47%) of these 19 COVID-19 patients showed a delayed or reduced T-cell response against the nucleoprotein and showed significant lower reactivity against the mitogen control stimulant. Interpretation: As none of the healthy controls had more than nine IFN-γ spot forming cells specific for the SARS-CoV-2 nucleoprotein, 10 or more spots was determined to be indicative for COVID-19 disease. The SARS-CoV-2 nucleoprotein ELISpot of patient samples taken more than three weeks after the start of symptoms showed a high diagnostic sensitivity for COVID-19 disease. T-cell response in a subgroup of COVID-19 patients was suboptimal and supports previous studies in which patients with COVID-19 were associated with a suppressed T-cell mediated immunity. Funding Statement: N/A Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The regional Medical Research Ethics Committees United approved the study (Nieuwegein, the Netherlands; MEC-U: NL73618.100.20).

Immune Status 'in Children with Beta Thalassemia' in Correlation 'with Iron Overload': Single Center Egyptian Study.

'Beta thalassemia is inherited hemoglobin disorder resulting in chronic hemolytic anemia that requires lifelong transfusion therapy'. 'Repeated blood transfusions and RBCs hemolysis are the main causes of iron overload', which in addition to immune abnormalities, are common predisposing factors to infections in patients with thalassemia. The Aim of this Work: The aim of this work was to study immune status including T lymphocyte subsets and serum immunoglobulin levels 'in children with beta- thalassemia in correlation with iron overload'. The present 'study was conducted on 40 children with beta thalassemia major under follow up at Hematology Unit, Pediatric Department, Tanta University' 'including 24 males and 16 females with mean' age value of 9. 22 ± 3.9 years and 20 'healthy children of matched age and sex as a control group'. All children included in the study were subjected to; 'complete blood count, Hb electrophoresis, serum iron status', T cell subsets including CD3, CD4 and CD8 and serum immunoglobulin levels including IgM, IgA and IgG. 'Pallor and jaundice were the most common presenting' clinical manifestations. Infective episodes 'were significantly higher in patients' compared with controls. There were significantly lower Hb, MCV and MCH levels and significantly higher WBCs and platelets counts, reticulocytes and lymphocytes percentage in patients than controls and no significant differences in MCHC between patients and controls. Serum ferritin and iron were 'significantly higher but TIBC was significantly lower in' patients than controls. CD3, CD4 and IgM were significantly lower but CD8, IgG, and IgA 'were significantly higher in patients than controls' with negative correlation between CD3, CD4, IgM and ferritin and positive correlation between CD8, IgG, IgA and ferritin. Iron overload can affect humeral and cell mediated immunity in patients with beta thalassemia with reduction of IgM, CD3 and CD4 and elevation of CD8, IgG, and IgA. Regular follow up of patients with beta thalassemia for detection of iron overload as it affects humeral and cell mediated immunity.

Circulating IL-6 and neopterin concentrations link cell-mediated immunity and tumor stage in patients with gastro-intestinal adenocarcinoma: relevance to the pituitary-adrenal axis and pituitary-thyroid axis

Abstract Although cortisol is a powerful modulator of the immune system and inhibits production of pro-inflammatory cytokines, adrenocorticotropic hormone (ACTH) levels do not correspond to the chronically elevated concentrations of cortisol in cancer patients. Thyroid stimulating hormone (TSH) has been shown to have an effect on immunological functions. Actually it is not known whether cortisol, TSH and IL-6 have an effect on tumor progression via modulation of cell mediated immunity in patients with gastrointestinal carcinoma. Sixty-seven gastrointestinal cancer patients and 42 cancer-free subjects with cholelithiasis as the control group, were included in the study. Serum ACTH, cortisol, TSH, thyroid hormones, IL-6, IL-10 and neopterin levels were measured. Diagnosis and pathological staging were confirmed by surgical intervention. Cortisol levels were correlated with IL-6 in cancer patients. In addition to elevated neopterin values, linear regression analysis revealed that serum neopterin was associated more strongly with the increase of cortisol rather than IL-6 levels in advanced stage carcinoma. Furthermore, neopterin also correlated with IL-6, IL-10, cortisol and TSH levels in advanced carcinoma cases. These data indicated that cortisol, IL-6 and neopterin values of cancer patients were influenced by the tumor presence and progression.

Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma

BackgroundCell mediated immunity is suppressed by systemic corticosteroids. Inhaled corticosteroids have been shown to affect parameters including bone metabolism, hypothalamus–pituitary adrenal axis, linear growth, and lead to the development of cataracts. However, it is unclear if high dose inhaled corticosteroid therapy affects cell mediated immunity. Study objectivesTo evaluate if asthma patients taking high dose inhaled corticosteroids chronically have reduced cell mediated immunity compared to asthma patients not taking inhaled corticosteroids. MethodsEighteen asthmatic subjects participated in this cross-sectional study. Cell mediated immunity was evaluated in nine patients who had been taking high dose inhaled corticosteroids for >6 months and nine patients not taking inhaled corticosteroids. Cell mediated immunity was evaluated by delayed type hypersensitivity (DTH) skin testing with intradermal placement of candida and tetanus antigens. ResultsThere was no significant difference in DTH skin test results between the high dose inhaled corticosteroid and no corticosteroid treated asthma group. ConclusionPatients with asthma taking high dose inhaled corticosteroids chronically (>6 months) did not have significantly greater impaired cell mediated immunity than patients not taking inhaled corticosteroids in this study.

Identification of Multiple HLA Class II Epitopes of Aspergillus Fumigatus by Generation of CD4+ T Cell Clones Recognizing the A. Fumigatus proteins Crf1 and Catalase1

AbstractAbstract 2332Invasive aspergillosis is a common and life-threatening complication in recipients of allogeneic stem cell transplantation. Patients are at risk in the neutropenic phase, but also after recovery of the neutrophil count there is an increased risk of developing invasive aspergillosis, probably caused by other defects in the innate immune system, or by impaired T cell mediated immunity after stem cell transplantation. In healthy individuals and in patients lymphoproliferative responses to crude Aspergillus extracts and recombinant antigens have been shown. Furthermore, patients after haploidentical stem cell transplantation were less susceptible to aspergillus infection when transferred with T cell lines generated against Aspergillus fumigatus. To facilitate the study of the role of T cell mediated immunity in aspergillus infection and develop new therapeutic strategies to prevent or treat invasive aspergillosis we aimed to identify T cell epitopes of Aspergillus fumigatus.Peripheral blood mononuclear cells (PBMC) of healthy individuals were stimulated with overlapping 15mer peptides of the Aspergillus fumigatus proteins Crf1 and Catalase1. Directly after stimulation no antigen specific T cells could be detected, however after stimulation with the complete peptide pool, IL-2 and IL-15 for 7 days and subsequent restimulation with peptide pulsed autologous PBMC an increase of activated T cells could be detected in half of the healthy donors, based on IFNγ production, CD154 (CD40 ligand) and CD137 expression. From 6 donors antigen specific CD4+ T cells were single cell sorted 4 hours after restimulation with the complete peptide pool using the IFNγ capture assay or by sorting the CD137+ CD4+ T cells 48 hours after restimulation with the complete peptide pool and cells were clonally expanded. The generated T cell clones were tested for Aspergillus peptide specificity against the complete peptide pool using ELISA to determine the IFNy and IL-4 production. Aspergillus peptide specific clones were further analyzed with subpools of the overlapping peptides, to identify the specific T cell epitope. These subpools are organized in a matrix to enable us to identify the recognized epitope directly from this analysis. Subsequently, the T cell clones were stimulated with the single recognized peptides to confirm the identified epitopes. Five different T cell epitopes of Crf1 were identified: one epitope at position 161–171, which was previously described, and four novel epitopes. For the Catalase1 protein we identified 7 different epitopes, which have not been described before. By using HLA-blocking monoclonal antibodies and an HLA-typed EBV-LCL panel we determined the HLA-restriction of the different T cell epitopes. Two Crf1 epitopes and three Catalase1 epitopes were HLA-DR restricted, and one of the Crf1 epitopes was presented by HLA-DP. The HLA-restriction of the other 6 identified epitopes has not yet been characterized. The T cell clones showed 3 different patterns of cytokine production. Some clones only produced IFNγ, some clones only IL-4 and others produced both IFNγ and IL-4.Twelve T cell epitopes in two different proteins of Aspergillus fumigatus, presented by various HLA class II molecules, were identified. The generated T cell clones showed a variable pattern of cytokine production. To evaluate whether all these epitopes are relevant for the immune response against aspergillosis, the specificity against Aspergillus fumigatus will be tested by incubating T cells and dendritic cells with inactivated fungus. If Aspergillus-specificity is demonstrated, these epitopes can be used to study T cell mediated immunity in patients with aspergillosis and be a first step towards new therapeutic options for invasive aspergillosis. Disclosures:No relevant conflicts of interest to declare.

Premature senescence of T lymphocytes from patients with β-thalassemia major

Several researches have demonstrated a suppressed cell mediated immunity in patients with β-thalassemia major. To know whether the premature aging of T cells is involved in abnormalities of cell mediated immunity, the biomarkers of immunosenescence including telomerase activity, apoptosis, and the expression of CD28 and CD95 were evaluated in T lymphocytes from β-thalassemia major patients. The ex vivo spontaneous apoptosis in CD4 + or CD8 + T cells from patients and healthy subjects was assessed by an in situ TdT mediated dUTP-biotin nick end labelling (TUNEL) assay after 24 h incubation in medium. Flow cytometric data revealed that lymphocytes from β-thalassemia patients were resistant to spontaneous apoptosis compared to the normal lymphocytes. Moreover, the percentages of TUNEL +CD4 + or TUNEL +CD8 + T cells from patients were significantly lower than those control cells. Quantitative determination of telomerase activity in resting and activated T cells was performed using the Telomeric Repeat Amplification Protocol (TRAP). The results showed a decreased telomerase activity of activated T cells in patients with thalassemia major compared to that in healthy controls. However, the percentages of CD8 +CD28 − and CD3 +CD95 + T lymphocytes were significantly higher in thalassemia patients, indicating the phenotypes associated with senescent T lymphocytes. These data provide evidences for the occurrence of accelerated aging of T cells in β-thalassemia major; possibly result in abnormal T cell function leading to suppressed cell mediated immunity.

Triggering of T Cell-Mediated Immune Responses by Allogenic Tumor Cell Vaccine in Patients with Oral Cancer

We investigated the immunomodulatory activity of allogenic whole tumor cell vaccine in oral cancer patients in vitro by two-color flow cytometry. Vaccine treatment significantly increased the expression of CD69 and HLA-DR in CD3+ T-cell subsets. The frequency of Interferon-gamma and Interleukin (IL)-2 expressing CD4+/CD8+ T-cell subsets was significantly higher with a concomitant reduction in IL-4 and IL-10 expressing T-cells in the vaccine treated group as compared with the untreated controls. Vaccine treatment significantly increased T-cell receptor (TCR), Vβ3, Vβ5 and Vβ8 usage. The results indicate that the allogenic whole tumor cell vaccine is able to trigger T-cell mediated immunity in patients with intraoral squamous cell carcinoma.

Susceptibility to fungal infections of nails in patients with primary antibody deficiency

Primary antibody deficiencies are rare diseases, which require early treatment with intravenous immunoglobulins to prevent fatal infections. The cell mediated immunity in patients with those immunodeficiencies remains unimpaired and usually they do not develop fungal infections. The aim of the study was to determine the susceptibility to fungal infections of nails in children with X-linked agammaglobulinaemia (XLA) and common variable immunedeficiency (CVID). Nail plate fragments collected from five patients with XLA and five with CVID were experimentally infected with a Candida albicans and Trichophyton mentagrophytes strains. The same procedures were carried out with the nails from a control group of 10 healthy volunteers. The intensity of the infection was evaluated on the basis of hyphe ingrown into the nail fragments. The main finding of the study was the increased susceptibility of antibody deficient patients to experimental nail infection with C. albicans and T. mentagrophytes.

Does stage of disease correlate with cell mediated immunity in patients with gastric cancer?

Does stage of disease correlate with cell mediated immunity in patients with gastric cancer?

A Study of Non-specific Cell Mediated Immunity in Patients with Esophageal Carcinoma : Assessment of Immunological Parameters

A Study of Non-specific Cell Mediated Immunity in Patients with Esophageal Carcinoma : Assessment of Immunological Parameters

Evaluation of T-cell mediated immunity in patients with prolonged viral hepatitis-B (PVH-B) treated with levamisole (L)

Evaluation of T-cell mediated immunity in patients with prolonged viral hepatitis-B (PVH-B) treated with levamisole (L)

T-antigen does not induce cell mediated immunity in patients with breast cancer

T-antigen does not induce cell mediated immunity in patients with breast cancer

T-antigen does not induce cell mediated immunity in patients with breast cancer.

A total of 80 subjects with benign and malignant breast disease and healthy controls were studied for reactivity to T-antigen, MN-antigens and phytohemagglutinin (PHA) using the lymphocyte blastogenesis assay. No differences were detected between controls and patients with benign or malignant breast disease in reactivity to T- and MN-antigens. Moreover, there was no differential response to T- and MN-antigens among patients with breast cancer. PHA reactivity, although similar between groups as a whole, was diminished in patients with advanced carcinoma. These findings indicate that T-antigen fails to induce cell mediated immunity in patients with breast cancer.

Increased cell mediated immunity in patients with chronic cutaneous trichophyton dermatophytosis

Increased cell mediated immunity in patients with chronic cutaneous trichophyton dermatophytosis

Non-specific cell mediated immunity in patients infected with Schistosoma mansoni in Kenya

Parameters of in vitro cell-mediated immunity (CMI) have been measured in the local Kenyan population infected with Schistosoma mansoni. Lymphocyte responses to the non-specific T cell mitogens Concanavalin A (Con A) and Phytohaemagglutinin (PHA) were reduced in about 60% of schistosomiasis patients. Lymphocytes from control uninfected, and S. mansoni-infected donors formed equal numbers of spontaneous rosettes with sheep red blood cells, indicating that there was no over-all reduction in the percentage numbers of T cells in the schistosomiasis patients.

Lymphocyte transformation in patients with breast cancer and the effect of surgery

Lymphocyte response to phytohemagglutinin (PHA) in vitro was subnormal in forty of fifty-one patients with breast cancer. After apparently successful surgery, lymphocyte response improved significantly in most of those in whom it had been previously impaired. It remained markedly subnormal in only five patients, two of whome subsequently died of metastases. This finding indicates that depressed cell mediated immunity in patients with breast cancer is the result of the malignant disease. Failure of the PHA response to revert to normal postoperatively may indicate a poor prognosis.

A clinical study of cell mediated immunity in patients with bronchial asthma (author's transl)

A clinical study of cell mediated immunity in patients with bronchial asthma (author's transl)