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At least 379 records · Page 21Linked to original sources
PubMed2001

Tumor-induced sensitivity to apoptosis in T cells from patients with renal cell carcinoma: role of nuclear factor-kappaB suppression.

Antitumor immunity fails to adequately develop in many cancer patients, including those with renal cell carcinoma (RCC). A number of different mechanisms have been proposed to explain the immune dysfunction observed in cancer patient T cells. Here we show that T cells from RCC patients display increased sensitivity to apoptosis. Tumor-infiltrating lymphocytes (TILs) display the most profound sensitivity, because 10-15% of those cells are apoptotic when assessed by terminal deoxynucleotidyltransferase-mediated nick end labeling in situ, and the number of apoptotic TILs further increases after 24 h of culture. Peripheral blood T cells from RCC patients are not directly apoptotic, although T lymphocytes derived from 40% of those individuals undergo activation-induced cell death (AICD) upon in vitro stimulation with phorbol myristate acetate and ionomycin. This is in contrast to T cells from normal individuals, which are resistant to AICD. TILs and peripheral blood T cells from RCC patients also exhibit impaired activation of the transcription factor, nuclear factor (NF)-kappaB. Additional findings presented here indicate that the heightened sensitivity of patient T cells to apoptosis may be tumor induced, because supernatants from RCC explants sensitize, and in some instances directly induce, normal T cells to apoptosis. These same supernatants also inhibit NF-kappaB activation. RCC-derived gangliosides may represent one soluble tumor product capable of sensitizing T cells to apoptosis. Pretreatment with neuraminidase, but not proteinase K, abrogated the suppressive effects of tumor supernatants on both NF-kappaB activation and apoptosis. Additionally, gangliosides isolated from tumor supernatants not only inhibited NF-kappaB activation but also sensitized T cells to AICD. These findings demonstrate that tumor-derived soluble products, including gangliosides, may contribute to the immune dysfunction of T cells by altering their sensitivity to apoptosis.

Apoptosis↗
PubMed1994

Factors associated with initiation of primary medical care for HIV-infected persons.

PURPOSE: To examine the degree of immune dysfunction of human immunodeficiency virus (HIV)-infected patients at the time of presentation and to identify factors associated with early and late initial primary medical care for HIV infection as measured by CD4+ lymphocyte count. PATIENTS AND METHODS: Two hundred fifty-one consecutive outpatients without prior primary care for HIV infection were assessed at a municipal hospital HIV intake clinic (derivation group). Sociodemographic and clinical variables were examined for their association with CD4+ cell count on presentation in bivariate and stepwise linear regression analyses. Variables of interest were examined in 123 similar patients at a second site to assess the generalizability of our findings (validation group). RESULTS: In the derivation group, 30% of patients presented for initial primary care with CD4+ cell counts less than 200/mm3, 51% had counts from 201/mm3 to 500/mm3, and only 19% had counts greater than 500/mm3. Twenty-seven percent of patients had delayed seeking medical care for longer than 1 year and 12%, for more than 2 years after an initial positive HIV serologic evaluation. Three variables were significant and independent predictors of CD4+ cell count on presentation: Haitian ethnicity (P = 0.05) and HIV-related symptoms (P = 0.005) were associated with lower CD4+ cell counts; and female sex (P = 0.009) was associated with higher CD4+ cell counts. With HIV-related symptoms excluded from the model, a history of cocaine use was also a significant predictor for higher CD4+ cell count (P = 0.02). In the validation group, which included few Haitians, results for female sex and HIV-related symptoms showed a similar association. CONCLUSIONS: Most HIV-infected patients presented for primary care with advanced immune dysfunction. A substantial percentage of patients waited over a year to initiate medical care after testing positive for HIV. Haitian patients presented later for primary HIV care as measured by CD4+ cell count. Women presented with significantly higher CD4+ cell counts than did men. Since few characteristics examined could clearly identify the majority of late-presenting HIV-infected patients, improved general and targeted efforts are needed to link all HIV-infected people with primary medical care before the development of advanced disease.

Adult↗
PubMedDate not supplied

Basal and lipopolysaccharide-inducible membrane alkaline phosphatase of lymphoid cells from mice with immune system dysfunctions.

The expression of membrane alkaline phosphatase (mAlPase) activity is an enzymatic marker of activated but not resting B cells which can be used on unseparated lymphoid cell suspensions. It is higher in lymphoid cell suspensions from mice with higher proportions of B cells (athymic mice) or with more activated B cells (autoimmune mice) than in those of control mice.

Alkaline Phosphatase↗
PubMed2003

Dysfunctional immune-privilege in morbid obesity: implications and effect of gastric bypass surgery.

BACKGROUND: Despite the epidemiological evidence linking obesity and cancer, there has never been a causal link. We believe the chronic inflammation present in obesity may predispose the obese to cancer through Fas-receptor over-expression and L-selectin under-expression in leukocytes, and elevated Fas ligand secretion in tumors affecting the morbidly obese. METHODS: Leukocytes from 25 patients having gastric bypass surgery were compared to 15 normal controls preoperatively and at 1, 3, 6, and 12 months postoperatively using flow cytometry to measure CD3, CD4, CD8, CD56, CD62 (L-selectin), CD69, and CD95 (Fas antigen) expression on T lymphocytes, B lymphocytes, natural killer cells, and neutrophils. RESULTS: The percentage of CD95 + T cells was significantly elevated from controls (69.4% vs 56%, P = 0.005). This difference persisted through 1 month postoperatively. Furthermore, expression of CD95 per cell, was significantly greater in these patients than that of the controls (80.2 vs 62.6 gmf, P = 0.018) preoperatively, and this continued to 1 month. Polymorphonuclear cells also displayed a similar elevation in CD95 gmf expression preoperatively (54.1 vs 40.7 gmf, P = 0.023) which normalized by 3 months. Natural killer cells did not display elevated numbers of CD95 gmf preoperatively, but they did experience a significant decline by 12 months. Additionally, there was significant reduction in the number of naiveT cells [(T cells without L-selectin (CD62L)], when compared to normals preoperatively (41.8% vs 51.3%, P = 0.001). There was no statistical difference between the postoperative patients and the controls by 3 months. CD69 was not different at baseline from controls in T or B cells, but there was a significant decrease by 12 months. CONCLUSION: The reduced expression of L-selectin combined with the elevated levels of CD95 suggests that morbid obesity predisposes patients to sites of immune privilege. This could be the mechanism for increased rates of cancer and wound infections seen in obesity. Surgically-induced weight loss eliminates these risk factors.

Adolescent↗
PubMed1990

The treatment of sepsis and other complications in the trauma patient.

Immediate complications of trauma and shock include right heart failure, acute respiratory distress syndrome, coagulopathy, brain edema, small bowel dysfunction, renal failure, and immune dysfunction. Nosocomial infections are also common in trauma patients. These infections are the combined result of a compromised host defense and various iatrogenic risk factors, including the use of percutaneous drainage tubes, malnutrition, the injudicious use of prophylactic antibiotics, and treatment staff hygiene. The use of prophylactic antibiotics appears to be unwarranted in head, maxillofacial, and neck injuries and is debatable in chest and soft-tissue wounds, fractures, and injuries of the peritoneal cavity. The use of antibiotics in small bowel and colon injuries is justified. Antibiotics are necessary in crush or avulsive injuries. Combination antibiotic therapy often results in multiple complications that may compound the patient's problems. Therefore, a single antibiotic with minimal side effects is the therapy of choice in the surgical intensive care unit.

Animals↗
PubMed1988

Immune regulation dysfunction in chronic persistent hepatitis.

The study included 19 children diagnosed clinically, biochemically, and by liver biopsy as having chronic persistent hepatitis. The following investigations were carried out: 1. detection of total T-lymphocytes, T-helper, and T-suppressor cells using monoclonal antibodies (OKT3, OKT4 and OKT8); 2. determination of HLA-A, B and DR antigens using the microcytotoxicity technique. The results were analysed in comparison with data from a normal control group. There are several important findings. First, low total T-lymphocytes with increased proportion of suppressor cells (P less than 0.001). Second, strong association between HLA-A1 antigen and CPH (Fisher exact = 0.000022). Third, significant association between the immunoregulatory dysfunction and A1 antigen (Fisher exact = 0.033). This observation suggests that a genetic component may influence susceptibility to CPH through an increased suppressor response.

Adolescent↗
PubMed2004

Interleukin-6 (IL-6) expression and natural killer (NK) cell dysfunction and anergy in heart failure.

Immune dysfunction has been postulated to play a role in the pathophysiology of chronic heart failure. We examined the relation between interleukin-6 (IL-6) production and natural killer (NK) cell dysfunction in patients with chronic heart failure. Sera and peripheral blood mononuclear cells (PBMCs) were collected from 82 patients with advanced heart failure. Levels of circulating NK cells and T cells were determined by flow cytometry. NK cell function was measured by standard cytotoxicity assays. IL-6 in supernatants of PBMC cultured in vitro was quantitated by an enzyme-linked immunosorbent assay. The levels of circulating NK cells were lower in patients with heart failure than in normal controls (p = 0.0037). NK cells from patients with heart failure also exhibited impaired cytolytic functions in the absence of stimuli and in response to IL-2 and IL-12 (p <0.0001 for all conditions). PBMCs from patients with heart failure produced higher levels of IL-6 in response to a T-cell stimulus than did PBMCs from healthy controls (p = 0.0012). The level of IL-6 produced by unstimulated PBMCs in patients with heart failure correlated with NK cell cytolytic impairment (p = 0.0012). These results demonstrated that PBMCs are a source of IL-6 in patients with heart failure. Production of IL-6 by PBMCs correlated with NK cell anergy to other cytokines that use signal transduction pathways that may be regulated by IL-6. These results support a model of cytokine-induced anergy in conditions that result in high systemic levels of IL-6.

Adult↗
PubMed2000

Mercuric chloride damages cellular DNA by a non-apoptotic mechanism.

Mercury is a xenobiotic metal that is well known to adversely affect the immune system, however, little is known as to the molecular mechanism. Recently, it has been suggested that mercury may induce immune dysfunction by triggering apoptosis in immune cells. Here, we studied the effects of Hg(2+) (HgCl(2)) on U-937 cells, a human cell line with monocytic characteristics. We found that these cells continued to proliferate when exposed to low doses of mercury between 1 and 5 microM. Using the single cell gel electrophoresis (SCGE) or 'comet' assay, we found that mercury damaged DNA at these levels. Between 1 and 50 microM Hg(2+), comet formation was concentration-dependent with the greatest number of comets formed at 5 microM mercury. However, the appearance of mercury-induced comets was qualitatively different from those of control cells treated with anti-fas antibody, suggesting that although mercury might damage DNA, apoptosis was not involved. This was confirmed by the finding that cells treated with 5 microM mercury were negative for annexin-V binding, an independent assay for apoptosis. These data support the notion that DNA damage in surviving cells is a more sensitive indicator of environmental insult than is apoptosis, and suggests that low-concentrations of ionic mercury may be mutagenic.

Annexins↗
PubMed2003

Effect of c-reactive protein and interleukins blood levels in postsurgery arginine-enhanced enteral nutrition in head and neck cancer patients.

OBJECTIVE: It is known that the immune system is frequently affected in patients with head and neck cancer. Although immune dysfunction could be multifactorial, this immune system may be modulated by specific nutritional substrates, such as arginine. The aim of our study was to evaluate the effect of enteral nutrition supplemented with arginine on c-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor (TNFalpha) in surgical head and neck cancer patients. DESIGN: Randomized trial. SETTING: Tertiary care. SUBJECTS: A population of 36 patients with oral and laryngeal cancer were enrolled. INTERVENTIONS: At surgery patients were randomly allocated to two groups: (a) patients receiving an enteral diet supplements with arginine and dietary fibre (group I, n=18); (b) patients receiving an isocaloric, isonitrogenous enteral formula (group II, n=18). Perioperatively and on postoperative day 5 the following parameters were evaluated: serum values of prealbumin, transferrin, albumin, total number of lymphocytes, interleukin 6, tumour necrosis factor alpha and c-reactive protein. RESULTS: The mean age was 59.6+/-10.9 y (two females/34 males). No significant intergroup differences in the trend of the three plasma proteins and weight were detected. CRP decreased in both groups (group I: 152.9+/-76.9 vs 68.9+/-82.5 mg/dl; P<0.05; and group II: 105.9+/-92 vs 43.6+/-59.1 mg/dl; P<0.05). Interleukin 6 did not change (group I: 16.3+/-12.3 vs 35.6+/-83.4 pg/ml; NS; and group II: 22.8+/-40 vs 9.9+/-17.7 pg/ml; NS). TNFalpha did not show any differences (group I: 4.6+/-1.6 vs 5.1+/-1.5 pg/ml; NS; and group II: 8.8+/-6.1 vs 5.8+/-1.7 pg/ml; NS). Lymphocytes increased in both groups (group I: 1405.6+/-517 vs 1634+/-529 x 10(6)/ml; P<0.05; and group II: 1355+/-696 vs 1561+/-541 x 10(6)/ml; P<0.05). CONCLUSIONS: Enhanced formula did not change IL6 and TNFalpha levels. Further studies are needed to determine whether route of nutrition or type of formula is the key in these patients.

Arginine↗
PubMed1994

Human immunodeficiency virus (HIV)-infected human blood monocytes and peritoneal macrophages have reduced anticryptococcal activity whereas HIV-infected alveolar macrophages retain normal activity.

Human immunodeficiency virus type 1 (HIV-1) infection causes immune dysfunction. Mononuclear phagocytes (MNP) are immune effector cells against some intracellular pathogens and reservoirs for HIV-1. This study determined effects of HIV-1 on MNP-mediated antifungal function. MNP from seronegative volunteers were inoculated with HIVBal or HIVIIIB. MNP were infected with an avirulent clone of Cryptococcus neoformans; 48 h later, MNP were lysed and yeasts were counted. Viral replication was determined by reverse transcriptase and by visualization of cytopathic effects. Monocytes and peritoneal macrophages exhibited reduced anticryptococcal activity 14 days after infection with HIVBal but retained normal activity when infected with HIVIIIB. Loss of anticryptococcal activity correlated with viral replication. Alveolar macrophages retained normal anticryptococcal activity whether infected with HIVBal or HIVIIIB. In vitro MNP-mediated antifungal activity may be altered by HIV-1 infection; this altered activity appears to depend on viral tropism, viral replication, and MNP tissue origin.

Cell Survival↗
PubMed2026

Proteomic analysis identifies pathways related to immune dysregulation in patients with hematologic malignancies after COVID-19 infection.

Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; however, because outcome groups were closely intertwined with initial COVID-19 severity, ICU admission, and systemic illness, and because multivariable adjustment was not performed due to the limited sample size, these patterns should be interpreted as severity- and outcome-associated profiles rather than independent trajectory-specific markers. Fatal cases showed evidence of dysregulated immune activation, whereas patients later classified as having long COVID exhibited broader suppression of immune-related pathways. In addition to immune alterations, pathways related to platelet activation and cardiac-related dysfunction were associated with adverse clinical trajectories. Enzyme-linked immunosorbent assay validation supported the association of selected proteins with outcome groups during acute infection. These findings provide a proteomic overview of COVID-19 in HM patients and offer a basis for future mechanistic studies and larger external validation cohorts.IMPORTANCEPatients with hematologic malignancies are highly vulnerable to severe coronavirus disease 2019 (COVID-19), acute death, and long COVID due to preexisting immune dysfunction. However, the proteomic signatures linked to adverse clinical trajectories remain poorly understood. Our serum proteomic study identifies distinct acute-phase immune profiles associated with different outcomes: broad immune suppression characterizes long COVID, while dysregulated immune activation is associated with fatal cases. Platelet activation and cardiac-related pathways are also linked to poor outcomes. These findings provide key molecular insights for this high-risk population, supporting future biomarker development, risk stratification, and targeted clinical management.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05683353.

Humans↗
PubMed1990

Two-color flow cytometric analysis of the expression of MAC and MHC class II antigens on macrophages during tumor growth.

Tumor-bearing host (TBH) macrophages (M phi) exhibit immune dysfunction that is concomitant with phenotypic changes. We examined M phi subpopulations by changes in the expression of surface antigens Mac-1, -2, -3, and Ia on normal and TBH peritoneal and splenic M phi. M phi were double-labeled and analyzed by flow cytometry to observe multiple expression of surface antigens. Tumor growth alters the multiple expression of these M phi markers. Peritoneal and splenic M phi had different Mac+ and Mac+Ia+ population percentages. In TBH, peritoneal M phi had decreased percentages of Mac-1+2+, Mac-1+3+, Mac-2+3+, and Mac+Ia+ M phi. This decrease correlated with functional changes in TBH M phi. In contrast, there was an increase in Mac-2-Ia- TBH peritoneal M phi. Previously undiscovered Mac-1+2-3- and Mac-1-2-3+ populations were found. In contrast to peritoneal M phi, there was an increase in the percentage of Mac-1+2+, Mac-1+3+, and Mac-2+3+ splenic TBH M phi but, like peritoneal M phi, there was a decrease in the percentage of Mac+Ia+ M phi. Also, TBH splenic M phi showed a smaller but more uniform antigen density than normal host splenic M phi. Tumor growth modulated phenotypic alterations in peritoneal and splenic M phi subpopulations. Combined with earlier functional studies of M phi subpopulations, these data suggested a relationship between changes in M phi phenotype and tumor-induced dysfunction of M phi-modulated immune activity.

Animals↗
PubMed1999

Shift in the IgG subclass distribution in patients with lung cancer.

Lung cancer patients have been reported to have generalized immune dysfunction of the cell-mediated immune response. In contrast, little is known about the humoral immune function in these patients. Therefore, we examined the IgG subclass distribution (IgG1-lgG4) in 67 lung cancer patients (23 adenocarcinoma, 29 squamous cell carcinoma, 15 small cell carcinoma), 13 patients with inflammatory lung diseases, seven patients with pulmonary metastasis and 23 healthy controls using a commercial available ELISA. We found a significant increase in the percentage of IgG1 in adenocarcinoma, compared with squamous cell and small cell lung carcinoma (P < 0.05). Small cell lung cancer patients showed an increase in IgG2, IgG3 and IgG4 compared with all other groups (P < 0.05, respectively). IgG1/lgG2, IgG1/lgG3 and IgG1/lgG4 ratios in adenocarcinoma were higher than in small cell lung cancer (P < 0.05). In the squamous cell carcinoma there was no difference in IgG subclass distribution compared to controls. Our study demonstrates that the different histological subtypes of lung carcinoma influence the IgG subclass distribution. Whether this phenomenon is the result of a direct influence on B-cell activity by the tumor needs further investigation.

Adenocarcinoma↗
PubMed1996

[A study on red blood cell immune function in patients with Guillain-Barré syndrome and multiple sclerosis].

In order to understand whether there is red blood cell (RBC) immune dysfunction and the relationship between RBC immune abnormality and clinical state in patients with multiple sclerosis (MS) and Guillain-Barré syndrome (GBS), RBC immune function and circulation immune complex (CIC) level were evaluated in patient with these two diseases by using RBC immune adhesion test. It was found that the rate of formation of red blood cell-C3b receptor-yeast rosette was significantly lower in patients with these two diseases before and after treatment than that in a control group (P < 0.01). The rate of formation of red blood cell-immune complex-yeast rosette and the CIC level in GBS group were notably higher than that in the control group (P < 0.05). Moreover, we observed that the immune functions in patients with severe GBS and active MS were different from those in patients with mild GBS and stable MS and the change of each immune index in GBS and MS patients was related with the degree of recovery and the clinical state. These results suggested that decreased capability of RBC immune adhesion in patients with GBC and MS may be one of factors causing these diseases.

Adolescent↗
PubMed1999

Severe injury triggers antigen-specific T-helper cell dysfunction.

Although it is established that post-injury immune dysfunction involves alterations in T-cell function, the effects of injury on T-cell function in vivo are poorly understood. This study uses a mouse injury model and an antigen immunization approach to investigate the influence of injury on antigen-specific T-helper cell function. We report here that injury triggered a significant reduction in antigen-specific T-helper-1 (Th1)-dependent IgG2a antibody formation, while IgM, IgG1, and IgE production was unchanged. In addition, injury caused a reduction in cytokine production (IL-2, IFNgamma and IL-10) by antigen-stimulated T-cells. We also demonstrate that interleukin 12 (IL-12), a cytokine that promotes Th1 cell differentiation, restored IgG2a antibody formation and corrected the injury-induced reduction in antigen-stimulated cytokine production. Taken together, these findings indicate that severe injury induces a dramatic reduction in Th1 cell function in vivo and suggest that therapies designed to restore Th1 cell function may be beneficial to the injured host.

Animals↗