NK cell compartment in patients with coronary heart disease

<p>Abstract</p> <p>Background</p> <p>Viral and bacterial infections have been considered as a risk factor for Coronary Heart Disease (CHD). NK cells, as a first line of defense against those infections, may play a role in CHD development. Thus, the main aim of our study was to determine NK cell compartment in patients with CHD undergoing coronary artery by-pass grafting.</p> <p>Results</p> <p>Ninety three patients with CHD were included into the study; the control group consisted of 49 healthy volunteers. As compared to controls, CHD patients had lower NK cytotoxic activity. CHD group had also a decreased absolute number and percentage of total NK cells and CD3-CD56dim cytotoxic NK subset. In addition, we observed tendency toward lower percentage of the CD3-CD56bright regulatory NK subset and CD3-CD56+IFN-γ+ cells in CHD patients.</p> <p>Conclusion</p> <p>These data indicate that CHD is associated with an impairment of NK cells compartment.</p

Nutrition, diet and immunosenescence

Ageing is characterized by immunosenescence and the progressive decline in immunity in association with an increased frequency of infections and chronic disease. This complex process affects both the innate and adaptive immune systems with a progressive decline in most immune cell populations and defects in activation resulting in loss of function. Although host genetics and environmental factors, such as stress, exercise and diet can impact on the onset or course of immunosenescence, the mechanisms involved are largely unknown. This review focusses on identifying the most significant aspects of immunosenescence and on the evidence that nutritional intervention might delay this process, and consequently improve the quality of life of the elderly

Age-Associated Decline in Dendritic Cell Function and the Impact of Mediterranean Diet Intervention in Elderly Subjects

Introduction: Aging is accompanied by increased susceptibility to infection and age-associated chronic diseases. It is also associated with reduced vaccine responses, which is often attributed to immunosenescence and the functional decline of the immune system. Immunosenescence is characterized by a chronic, low-grade, inflammatory state termed inflammaging. Habitants of Mediterranean (MED) regions maintain good health into old age; often attributed to MED diets. Hypothesis: Adoption of a MED-diet by elderly subjects, in Norfolk (UK), may improve immune responses of these individuals and in particular, dendritic cell (DC) function. Experimental approach: A total of 120 elderly subjects (65–79 years old) recruited onto the Nu-AGE study, a multicenter European dietary study specifically addressing the needs of the elderly, across five countries, and were randomized to the control or MED-diet groups, for one year. Blood samples were taken pre- and post-intervention for DC analysis and were compared with each other, and to samples obtained from 45 young (18–40 years old) subjects. MED-diet compliance was assessed using high performance liquid chromatography-with tandem mass spectrometry analysis of urine samples. Immune cell and DC subset numbers and concentrations of secreted proteins were determined by flow cytometric analysis. Results: As expected, reduced myeloid DC numbers were observed in blood samples from elderly subjects compared with young. The elevated secretion of the adipokine, resistin, after ex vivo stimulation of peripheral blood mononuclear cells from elderly subjects, was significantly reduced after MED-diet intervention. Conclusion: This study provides further evidence of numerical and functional effects of aging on DCs. The MED-diet showed potential to impact on the aging immune cells investigated and could provide an economical approach to address problems associated with our aging population

Baseline Levels of Influenza-Specific CD4 Memory T-Cells Affect T-Cell Responses to Influenza Vaccines

BACKGROUND: Factors affecting immune responses to influenza vaccines have not been studied systematically. We hypothesized that T-cell and antibody responses to the vaccines are functions of pre-existing host immunity against influenza antigens. METHODOLOGY/PRINCIPAL FINDINGS: During the 2004 and 2005 influenza seasons, we have collected data on cellular and humoral immune reactivity to influenza virus in blood samples collected before and after immunization with inactivated or live attenuated influenza vaccines in healthy children and adults. We first used cross-validated lasso regression on the 2004 dataset to identify a group of candidate baseline correlates with T-cell and antibody responses to vaccines, defined as fold-increase in influenza-specific T-cells and serum HAI titer after vaccination. The following baseline parameters were examined: percentages of influenza-reactive IFN-gamma(+) cells in T and NK cell subsets, percentages of influenza-specific memory B-cells, HAI titer, age, and type of vaccine. The candidate baseline correlates were then tested with the independent 2005 dataset. Baseline percentage of influenza-specific IFN-gamma(+) CD4 T-cells was identified as a significant correlate of CD4 and CD8 T-cell responses, with lower baseline levels associated with larger T-cell responses. Baseline HAI titer and vaccine type were identified as significant correlates for HAI response, with lower baseline levels and the inactivated vaccine associated with larger HAI responses. Previously we reported that baseline levels of CD56(dim) NK reactivity against influenza virus inversely correlated with the immediate T-cell response to vaccination, and that NK reactivity induced by influenza virus depended on IL-2 produced by influenza-specific memory T-cells. Taken together these results suggest a novel mechanism for the homeostasis of virus-specific T-cells, which involves interaction between memory helper T-cells, CD56(dim) NK and DC. SIGNIFICANCE: These results demonstrate that assessment of baseline biomarkers may predict immunologic outcome of influenza vaccination and may reveal some of the mechanisms responsible for variable immune responses following vaccination and natural infection

The impact of ageing on natural killer cell function and potential consequences for health in older adults

Forming the first line of defence against virally infected and malignant cells, natural killer (NK) cells are critical effector cells of the innate immune system. With age, significant impairments have been reported in the two main mechanisms by which NK cells confer host protection: direct cytotoxicity and the secretion of immunoregulatory cytokines and chemokines. In elderly subjects, decreased NK cell activity has been shown to be associated with an increased incidence and severity of viral infection, highlighting the clinical implications that age-associated changes in NK cell biology have on the health of older adults. However, is an increased susceptibility to viral infection the only consequence of these age-related changes in NK cell function? Recently, evidence has emerged that has shown that in addition to eliminating transformed cells, NK cells are involved in many other biological processes such as immune regulation, anti-microbial immune responses and the recognition and elimination of senescent cells, novel functions that involve NK-mediated cytotoxicity and/or cytokine production. Thus, the decrease in NK cell function that accompanies physiological ageing is likely to have wider implications for the health of older adults than originally thought. Here, we give a detailed description of the changes in NK cell biology that accompany human ageing and propose that certain features of the ageing process such as: (i) the increased reactivation rates of latent Mycobacterium tuberculosis, (ii) the slower resolution of inflammatory responses and (iii) the increased incidence of bacterial and fungal infection are attributable in part to an age-associated decline in NK cell function

NK cells in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma after cessation of intensive chemotherapy

Intensive, combination chemotherapy for malignant diseases causes a profound immunosuppression, which persists for the whole treatment period and after its completion. Impairment of the NK cells status may increase the risk of severe, disseminated infections and cancer. The aim of the study was the investigation of recovery of NK cells after cessation of intensive chemotherapy in children with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). The number of CD3 - CD16+CD56+ cells in peripheral blood and NK cell cytotoxic activity were assessed in 23 children with ALL and 7 children with NHL at 2 weeks and 12 months after the cessation of intensive chemotherapy and in 15 healthy subjects. Absolute leukocyte, lymphocyte and NK cell counts and the percentage of NK cells in children with ALL were significantly lower than in control subjects both at 2 weeks and 12 months after intensive treatment. Additionally, the absolute numbers of leukocytes and lymphocytes decreased significantly after 12 months of observations in comparison to the initial time-point. In children with non-Hodgkin lymphoma at 2 weeks and 12 months after intensive treatment only absolute lymphocyte counts were significantly lower than values in healthy children. The absolute number, the percentage and cytotoxic activity of NK cells were comparable with values in the control group both at the initial and at the last time-point. The occurrence of infections during the 12 months of observations in patients with ALL were higher than in children with NHL and as many as eight of them were hospitalized because of severe infections. The differences between the ALL and NHL patients may be connected with the milder immunosuppressive effect of chemotherapy in the non-Hodgkin lymphoma since the children recovered from acute lymphoblastic leukemia remain with persistent defect of NK cells. It is then recommended that ALL children should be supervised with respect to an increased susceptibility to infections