| 1. |
- Cherfan, P, et al.
(author)
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Effects of simvastatin on human T cells in vivo
- 2007
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 193:1, s. 186-192
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Journal article (peer-reviewed)abstract
- Objective: The use of statins has shown several anti-inflammatory actions, including modulatory effects on T cells in vitro. Since the effects on human T cells in vivo are less clarified, our aim was to investigate the effects of simvastatin on human T cells in vivo and ex vivo. Methods and results: A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. The serum levels of C-reactive protein (CRP) were significantly reduced by simvastatin. The proportions of CD4+ and CD8+ T cell subsets expressing early (CD25) or late (HLA-DR) activation markers, as assessed by flow cytometry, were not changed by simvastatin. However, simvastatin tended to increase the density of HLA-DR and L-selectin per CD8+ T cell. The T helper(h)1/Th2 response was evaluated by stimulatory assays followed by intra-cellular staining of interferon-γ and interleukin-4. Simvastatin treatment did not affect the Th1 response but the results indicated a potential to suppress Th2. Conclusion: Simvastatin treatment resulted in a few discrete changes as regards peripheral T cells. However, the findings do not provide evidence that simvastatin-induced anti-inflammatory actions are related to any significant modulatory effects on human T cells in clinically healthy men with hypercholesterolemia. © 2006 Elsevier Ireland Ltd. All rights reserved.
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| 2. |
- Jonasson, Lena, et al.
(author)
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Expansion of peripheral CD8+ T cells in patients with coronary artery disease : Relation to cytomegalovirus infection
- 2003
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 254:5, s. 472-478
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Journal article (peer-reviewed)abstract
- Objectives. The nature of the immune response in coronary artery disease (CAD) is not fully defined. One pathogen that has been linked to atherogenesis, cytomegalovirus (CMV). is known to exert strong and long-lasting effects on peripheral T cells. In the present study, we investigated the effect of prior CMV infection on the immune system in CAD patients. Subjects. Patients with stable angina and angiographically verified CAD (n = 43) and clinically healthy controls (n = 69) were included. Methods. The expression of CD57 and CD28 on peripheral CD4+ and CD8+ T cells was evaluated with three-colour flow cytometry. The findings were related to serological markers of inflammation, T-cell activation and CMV seropositivity. Results. An expansion of CD8+ T cells expressing CD57 but lacking CD28 was seen in the patient group. The numbers of CD8+CD57+ and CD8+ CD28- T-cell subsets were independently related to CMV seropositivity (P < 0.001) but also to CAD per se (P < 0.05). Serum concentrations of C-reactive protein (CRP) and soluble interleukin-2 receptor (sIL-2R) were elevated in the patients but not related to CMV or CD8 + T-cell subsets. Conclusion. A pronounced shift in peripheral T-cell homeostasis was observed in CAD patients. Primarily CMV infection but also CAD per se contributed to the expansion of CD8+ T-cell subsets. The T-cell changes were not related to a systemic inflammatory response but should rather be considered as markers of a chronic antigen exposure and/or immunosenescence in CAD.
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| 3. |
- Ross, Owen A., et al.
(author)
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Mitochondrial DNA damage in lymphocytes : a role in immunosenescence?
- 2002
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In: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 37:2-3, s. 329-340
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Journal article (peer-reviewed)abstract
- An age-related increase of DNA damage/mutation has been previously reported in human lymphocytes. The high copy number and mutation rate make the mtDNA genome an ideal candidate for assessing damage and to act as a potential biomarker of ageing. In the present study, two assays were developed to evaluate the level of mtDNA4977 and the accumulation of point mutations with age. A competitive polymerase chain reaction (PCR) methodology incorporating three primers was used to detect and quantify the levels of mtDNA4977 and a novel heteroduplex reference strand conformational analysis (RSCA) technique was used to analyse the accumulation of point mutations. The assays were applied to an in vitro model of T cell ageing and ex vivo DNA samples from an elderly cohort of subjects and a younger control group. The mtDNA4977 was detected in all the DNA samples examined but only a very low concentration was observed and no age-related increase or accumulation was observed. No accumulation of point mutations was identified using RSCA within the T cell clones as they were aged or the ex vivo lymphocytes from the elderly cohort. A higher level of variation was observed within the ex vivo DNA samples, verifying the high resolution of RSCA and its ability to identify different mtDNA species, although no correlation with age was observed. The low level of mtDNA damage observed with respect to the ex vivo lymphocyte DNA samples within this study may be due in part to the high turnover of blood cells/mtDNA, which may inhibit the accumulation of genetically abnormal mtDNA that may play a role in immunosenescence. A similar explanation may also apply to the in vitro model of T cell ageing if the vast majority of the cells are replicating rather than entering senescence.
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| 4. |
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| 5. |
- Strindhall, Jan, et al.
(author)
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The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals : the Swedish HEXA immune study
- 2013
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In: Age (Omaha). - : Springer Netherlands. - 0161-9152 .- 1574-4647. ; 35:3, s. 985-991
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Journal article (peer-reviewed)abstract
- The Swedish OCTO and NONA immune longitudinal studies were able to identify and confirm an immune risk profile (IRP) predictive of an increased 2-year mortality in very old individuals, 86–94 years of age. The IRP, was associated with persistent cytomegalovirus infection and characterized by inverted CD4/CD8 ratio and related to expansion of terminally differentiated effector memory T cells (TEMRA phenotype). In the present HEXA immune longitudinal study, we have examined a younger group of elderly individuals (n = 424, 66 years of age) in a population-based sample in the community of Jönköping, Sweden, to examine the relevance of findings previously demonstrated in the very old. Immunological monitoring that was conducted included T cell subsets and CMV-IgG and CMV-IgM serology. The result showed a prevalence of 15 % of individuals with an inverted CD4/CD8 ratio, which was associated with seropositivity to cytomegalovirus and increases in the level of TEMRA cells. The proportion of individuals with an inverted CD4/CD8 ratio was significantly higher in men whereas the numbers of CD3+CD4+ cells were significantly higher in women. In conclusion, these findings are very similar to those previously found by us in the Swedish longitudinal studies, suggesting that an immune profile previously identified in the very old also exists in the present sample of hexagenerians. Therefore, it will be important to examine clinical parameters, including morbidity and mortality, to assess whether the immune profile also is a risk profile associated with higher mortality in this sample of hexagenerians.
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| 6. |
- Forsey, R.J., et al.
(author)
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Plasma cytokine profiles in elderly humans
- 2003
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In: Mechanisms of Ageing and Development. - 0047-6374 .- 1872-6216. ; 124:4, s. 487-493
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Conference paper (other academic/artistic)abstract
- It is known that as we age, immune dysregulation often occurs, leading to failing health, and increased susceptibility to a number of different diseases. In this study we have investigated plasma cytokine profiles in order to identify immune markers of ageing. Plasma samples were obtained from 138 participants of the Swedish longitudinal NONA study (aged 86, 90 and 94 years) and 18 healthy Swedish volunteers (aged between 32 and 59 years). Our results show significantly increased levels of the pro-inflammatory cytokine interleukin-6 (P<0.0001) and soluble intercellular adhesion molecule-1 (P<0.0001) in the elderly group. The anti-inflammatory cytokine interleukin-10 did not alter with age whereas active (naturally processed) transforming growth factor-ß levels were significantly (P<0.0001) increased in the elderly group. No difference was observed between males and females. These data suggest that there are measurable changes in cytokine profiles with ageing with increased levels of potentially harmful molecules, which may contribute to immune alterations and declining health in the elderly population. © 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 7. |
- Hadrup, SR, et al.
(author)
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Longitudinal studies of clonally expanded CD8 T cells reveal a reperoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly
- 2006
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In: The Journal. Immmunology. ; , s. 2645-2653
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Journal article (peer-reviewed)abstract
- The age-associated decrease in functionality of the human immune system is thought to have a negative impact on the capacity to provide protection against infection, in turn leading to in-creased incidence of mortality. In a previous longitudinal study of octogenarians, we identi-fied an immune risk phenotype (IRP) in the very elderly defined by an inverted CD4/CD8 ra-tio, which was associated with increased mortality and persistent CMV infection. In this study, we analyzed the CD8 clonal composition of nonagenarians and middle-aged individu-als. An increased number of CD8 T cell clones was observed in the nonagenarians, and was associated with CMV-seropositivity. Surprisingly, CMV-seropositive nonagenarians with the IRP had a significantly lower number of clones compared with non-IRP individuals. The de-crease in clone numbers in IRP individuals was associated with shorter survival time. MHC/peptide multimer staining indicated that the frequency of CMV-specific T cells was higher in nonagenarians than in the middle-aged, but the ratio of functionally intact cells was significantly lower. The lowest ratio of functional CMV-specific T cells was found in an IRP individual. A thorough longitudinal analysis of the CMV-specific T cells in nonagenarians showed a stable pattern with respect to frequency, phenotype, and clonal composition. We hypothesize that the number of different CD8 T cell clonal expansions increases as the indi-vidual ages, possibly, as a compensatory mechanism to control latent infections, e.g., CMV, but eventually a point is reached where clonal exhaustion leads to shrinkage of the CD8 clonal repertoire, associated with decreased survival
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| 9. |
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| 10. |
- Jonasson, Lena, et al.
(author)
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Low serum ß-carotene reflects immune activation in patients with coronary artery disease
- 2003
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In: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - 0939-4753 .- 1590-3729. ; 13:3, s. 120-125
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Journal article (peer-reviewed)abstract
- Background and Aim: Low serum levels of antioxidant vitamins are associated with coronary artery disease (CAD). An immunomodulatory effect of antioxidants has been proposed. The aim of the study was to investigate whether an increased immune response in CAD patients was associated with suppressed circulating levels of antioxidant vitamins. Methods and Results: Forty-four men with stable angina and angiographically verified CAD were included as well as 69 healthy controls. T cell subsets in peripheral blood were quantified by 3-colour flow cytometry. C-reactive protein (CRP), soluble interleukin-2 receptor (sIL-2R) and the lipophilic antioxidants a-tocopherol, ß-carotene and lycopene were determined in serum. Compared with controls, patients had signs of an enhanced inflammatory activity assessed by significantly increased levels of CRP, sIL-2R and CD4+CD25+T cell subsets. Patients also had significantly lower ß-carotene and lycopene levels whereas a-tocopherol levels did not differ. The increased inflammatory/immune parameters in patients showed a significant inverse relationship to serum ß-carotene but not to lycopene or a-tocopherol. Conclusions: Low serum ß-carotene in CAD patients reflects activation of the immune system. Inflammation should be considered as an important confounding factor when analysing data on ß-carotene and CAD. © 2003, Medikal Press.
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