| 1. |
- Wikby, A, et al.
(författare)
-
An immune risk phenotype, cognitive impairment and survival in very late life: The impact of alosta-tic load in Swedish Octo- and Nongenarian humans
- 2005
-
Ingår i: Journal Gerontology: Biological Science. ; , s. 556-565
-
Tidskriftsartikel (refereegranskat)abstract
- In the previous OCTO longitudinal study, we identified an immune risk pheno-type (IRP) of high CD8 and low CD4 numbers and poor proliferative response. We also demonstrated that cognitive impairment constitutes a major predictor of nonsurvival. In the present NONA longitudinal study, we simultaneously exam-ine in a model of allostatic load IRP and compromised cognition in 4-year survival in a population-based sample (n = 138, 86-94 years). Immune system measure-ments consisted of determinations of T-cell subsets, plasma interleukin 6 and cy-tomegalovirus and Epstein-Barr virus serology. Interleukin 2 responsiveness to concanavalin A, using data from the previous OCTO (octogenarians) immune study, hereafter OCTO immune, was also examined. Cognitive status was rated using a battery of neuropsychological tests. Logistic regression indicated that the IRP and cognitive impairment together predicted 58% of observed deaths. IRP was associated with late differentiated CD8+CD28-CD27- cells (p < .001), de-creased interleukin 2 responsiveness (p < .05) and persistent viral infection (p < .01). Cognitive impairment was associated with increased plasma interleukin 6 (p < .001). IRP individuals with cognitive impairment were all deceased at the fol-low-up, indicating an allostatic overload.
|
|
| 2. |
|
|
| 3. |
- Sjöwall, J, et al.
(författare)
-
Innate immune responses in Lyme borreliosis : enhanced tumour necrosis factor-alpha and interleukin-12 in asymptomatic individuals in response to live spirochetes
- 2005
-
Ingår i: Clinical and Experimental Immunology. - Oxford : Blackwell Publishing. - 0009-9104 .- 1365-2249. ; 141:1, s. 89-98
-
Tidskriftsartikel (refereegranskat)abstract
- Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in DCs and IL-1 beta, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-alpha-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease.
|
|
| 4. |
- Strindhall, J, et al.
(författare)
-
No Immune Risk Profile among individuals who reach 100 years of age: findings from the Swedish NONA immune longitudinal study
- 2007
-
Ingår i: Exp Gerontol.. ; 42:8, s. 753-761
-
Tidskriftsartikel (refereegranskat)abstract
- In the present NONA immune longitudinal study, we investigate the previously identified Immune Risk Profile (IRP), defined by an inverted CD4/CD8 ratio and associated with persistent cytomegalovirus infection and increased numbers of CD8+CD28- cells, relative 6-year survival and age in NONA individuals. These subjects have now reached age 92, 96, and for the first time in this study, 100 years at follow-up. A 55 year old middle-aged group was used for comparison. Immunological monitoring included the analysis of numbers of lymphocytes and neutrophils, the T-cell subsets CD3+CD4+, CD3+CD8+, CD8+CD28+, CD8+CD28-, and the CD4/CD8 ratio. Longitudinal data were analysed by multivariate analyses of variance (MANOVA) from four measurement occasions at 2-year inter-intervals. One-way ANOVA was used for cross-sectional comparisons at baseline and the 6-year follow-up. The results confirmed the importance of the IRP as a major predictor of mortality in this population of very old. Moreover, the results suggested that survival to the age of 100 years is associated with selection of individuals with an "inverted" IRP that was stable across time, i.e., maintenance of a high CD4/CD8 ratio and low numbers of CD8+CD28- cells. The results underlines the importance of a longitudinal study design in dissecting immune parameters predictive of survival and show for the first time that centenarian status is associated with avoidance of the IRP over at least the previous 6 years and probably throughout life.
|
|
| 5. |
- Wikby, A, et al.
(författare)
-
The immune risk phenotype is associated with Il-6 in the terminal decline stage: Findings from the Swedish NONA immune longitudinal study of very late life functioning
- 2006
-
Ingår i: Mechanisms Ageing and Development. - : Elsevier. ; 127:8, s. 695-704
-
Tidskriftsartikel (refereegranskat)abstract
- In the present NONA immune longitudinal study, we further examine the previously identi-fied T cell immune risk phenotype (IRP), relative inflammatory activity, morbidity and 2-year mortality in very old individuals >90 years. T-cell subsets as well as the inflammatory mark-ers IL-6, IL-10, C-reactive protein, transthyretin and albumin were evaluated. IRP and low-grade inflammation predicted 57% of observed deaths and 97% of survival over 2 years, and was not significantly affected by individuals' health status, suggesting that the physiological ageing processes of T-cell immunosenescence and low-grade inflammation are of primary importance in late life survival. IRP non-survivors showed only a minor inflammatory activity at baseline, but had in contrast to survivors developed increased activity at follow-up. The re-sults suggest a sequence of stages for IRP individuals that begin with acquisition of CMV in-fection in earlier life, followed by generation of CD8+CD28- cells to control persistent CMV infection and eventually the development of an IRP. Intriguingly, we also found that rare in-dividuals moved out of the IRP category by a process of immune suppression, including in-creases in IL-6 and IL-10 and decreases in the number of CD3+CD8+CD28- cells. The fur-ther characterisation of these exceptional individuals may allow insight into remedial ap-proaches for those who remain in the IRP category until death
|
|
| 6. |
- Henningsson, Anna J., et al.
(författare)
-
Complement activation in Lyme neuroborreliosis : increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS
- 2007
-
Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 183:1-2, s. 200-207
-
Tidskriftsartikel (refereegranskat)abstract
- A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.
|
|
| 7. |
- Mjösberg, Jenny, et al.
(författare)
-
Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ T-regs in human second trimester pregnancy is induced by progesterone and 17 beta-estradiol
- 2009
-
Ingår i: Journal of Reproductive Immunology(ISSN 0165-0378), vol 81, issue 2. - : Elsevier BV. ; , s. 160-161
-
Konferensbidrag (refereegranskat)abstract
- CD4+CD25high regulatory T cells (Tregs) are implicated in maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim was to determine the frequency, phenotype and function of circulating Tregs in second trimester human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expression of Foxp3, CD127 and HLA-DR, as determined by multi-color flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from non-pregnant women. By co-culturing FACS-sorted Tregs and autologous CD4+CD25- responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as non-pregnant women in terms of suppressing IL-2, TNF-α and IFN-γ secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Further, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need re-evaluation.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Strindhall, J., et al.
(författare)
-
No Immune Risk Profile among individuals who reach 100 years of age : Findings from the Swedish NONA immune longitudinal study
- 2007
-
Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 42:8, s. 753-761
-
Tidskriftsartikel (refereegranskat)abstract
- In the present NONA immune longitudinal study, we investigate the previously identified Immune Risk Profile (IRP), defined by an inverted CD4/CD8 ratio and associated with persistent cytomegalovirus infection and increased numbers of CD8+CD28- cells, relative 6-year survival and age in NONA individuals. These subjects have now reached age 92, 96, and for the first time in this study, 100 years at follow-up. A 55 year old middle-aged group was used for comparison. Immunological monitoring included the analysis of numbers of lymphocytes and neutrophils, the T-cell subsets CD3+CD4+, CD3+CD8+, CD8+CD28+, CD8+CD28-, and the CD4/CD8 ratio. Longitudinal data were analysed by multivariate analyses of variance (MANOVA) from four measurement occasions at 2-year inter-intervals. One-way ANOVA was used for cross-sectional comparisons at baseline and the 6-year follow-up. The results confirmed the importance of the IRP as a major predictor of mortality in this population of very old. Moreover, the results suggested that survival to the age of 100 years is associated with selection of individuals with an "inverted" IRP that was stable across time, i.e., maintenance of a high CD4/CD8 ratio and low numbers of CD8+CD28- cells. The results underlines the importance of a longitudinal study design in dissecting immune parameters predictive of survival and show for the first time that centenarian status is associated with avoidance of the IRP over at least the previous 6 years and probably throughout life. © 2007 Elsevier Inc. All rights reserved.
|
|
