| 1. |
- Bengnér, Malin, et al.
(författare)
-
Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity.
- 2014
-
Ingår i: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:2, s. 571-582
-
Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) infection induces profound changes in different subsets of the cellular immune system. We have previously identified an immune risk profile (IRP) where CMV-associated changes in the T cell compartment, defined as a CD4/CD8 ratio < 1, are associated with increased mortality in elderly people. Since natural killer (NK) cells have an important role in the defense against viral infections, we examined whether the expansion of CD8 + T cells seen in individuals with CD4/CD8 ratio < 1 is coupled to a parallel skewing of the NK cell compartment. A number of 151 subjects were examined with CMV serology and a flow cytometry panel for assessment of T cell and NK cell subsets. CMV-seropositive individuals had higher frequencies of CD57 + and NKG2C + NK cells and lower frequencies of NKG2A + NK cells, in line with a more differentiated NK cell compartment. Intriguingly, however, there was no correlation between CD4/CD8 ratio and NK cell repertoires among CMV-seropositive donors, despite the profound skewing of the T cell compartment in the group with CD4/CD8 ratio < 1. Conversely, donors with profound expansion of NK cells, defined as NKG2C + NK cells with high expression of CD57 and ILT-2, did not display more common changes in their T cell repertoire, suggesting that NK cell expansion is independent of the T cell-defined IRP. Altogether, these results indicate that the effect of CMV on CD8 T cells and NK cells is largely nonoverlapping and independent.
|
|
| 2. |
- Nilsson, Bengt-Olof, 1954-, et al.
(författare)
-
Antinuclear antibodies in the oldest-old women and men
- 2006
-
Ingår i: Journal of Autoimmun. - : Elsevier. ; 27:4, s. 281-288
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the prevalence of antinuclear antibodies (ANA) in very old individuals (>/=86years of age) with healthy younger (18-68years) blood donors (n=200) regarding gender, health status, ratio of circulating CD4/CD8 cells and cytomegalovirus (CMV) serology. Frozen plasma was used for ANA detection in two study groups, i.e. 'OCTO' (97 persons aged 86-92years, 65% women) and 'NONA' (136 persons aged 86-95years, 70% women). OCTO participants were recruited on the basis that they were healthy or moderately healthy according to a selection protocol. No exclusion criteria regarding health status were applied in the NONA sample. The prevalence of ANA was significantly higher in the oldest-old samples compared to blood donors. There was no association between health status and the presence of ANA in the oldest-old. The difference across age was most pro-nounced in men, with low levels at younger age, whereas the prevalence among the oldest-old men reached similar levels as in women. There were no associations between the presence of ANA and CD4/CD8 ratio or with CMV status in the oldest-old. Our findings confirm an in-creased prevalence of ANA in the oldest-old, and emphasize the importance of taking gender and age into consideration when evaluating ANA.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Nilsson, Bengt-Olof, et al.
(författare)
-
Morbidity does not influence the T-cell immune risk phenotype in the elderly : Findings in the Swedish NONA Immune Study using sample selection protocols
- 2003
-
Ingår i: Mechanisms of Ageing and Development. - : Elesvier. - 0047-6374 .- 1872-6216. ; 124:4, s. 469-476
-
Tidskriftsartikel (refereegranskat)abstract
- A critical issue in our understanding of ageing and the immune system refers to the health status of the population from which inferences are drawn. The commonly used SENIEUR protocol, selecting individuals representing 'normal ageing' has recently been under debate because a substantial amount of individuals with various health problems are excluded. The aim of the present study was to investigate the influence of morbidity on immune parameters and to evaluate the associations with the T-cell immune risk phenotype (IRP), related to cytomegalovirus (CMV) seropositivity by applying the SENIEUR protocol and the OCTO-Immune protocol in the unselected population based sample (n = 138) of oldest-olds, participating in the Swedish NONA Immune Study. The SENIEUR protocol excluded over 90% of the sample whereas the OCTO-Immune protocol excluded almost 65% of the sample. Three independent groups, very healthy (SENIEUR), moderately healthy (OCTO-Immune) and frail (non-SENIEUR/non-OCTO-Immune) were created. Flow cytometry studies on lymphocyte sub-populations revealed no significant difference in CD4/CD8 ratio, CD3+CD4-CD8+, CD3+CD4+CD8-, CD8+CD57+CD28-, CD8+CD56+CD57- or CD8+CD56+CD57+ between the very healthy, moderately healthy and the frail subsamples. Our findings indicate that morbidity does not significantly influence the T-cell immune risk profile in the elderly, and we suggest the inclusion of broader samples in future immunogerontological studies.
|
|
| 6. |
- Nilsson, Bengt-Olof, 1954-, et al.
(författare)
-
The Immune Risk Phenotype and IL-6 among Nonagenarians and Associations with Morbidity and Mortality : Findings from the Swedish NONA Immune Longitudinal Study
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this NONA immune longitudinal study, we examine 4-year mortality in relation to a set of laboratory parameters, morbidity and cause of death in a population-based sample of oldest-old individuals (n=138). Four groups were constructed based on levels for the CD4/CD8 ratio (above or below one = IRP, immune risk phenotype group) and levels for IL-6 (below or above the median 3.15 pg/mL). 4-year mortality was higher in the “IRP” group (73 %), the “IL-6” group (64 %), and the “Double risk group” (82 %) compared with the “No risk” group (29 %; p-values between .005 and .000). Cognitive dysfunction and dementia were more common in the two groups with elevated IL-6 levels (p-values between .014 and .001), whereas cardiovascular disease tended (p = .081) to be associated with both “IRP” and “IL-6” groups. The most common cause of death was related to cardio- and cerebrovascular disease (59 %,), followed by infection in 15 % of the cases and cancer in 7 %. Despite their strong associations with 4-year mortality, neither IRP nor IL-6 could be linked to any specific cause of death, possibly because both IRP and IL-6 are multi-factorial risk factors, being associated with several different diseases and mechanisms which cause death.
|
|
| 7. |
- Nilsson, Bengt-Olof, 1954-
(författare)
-
The Immune System in the Oldest-Old : Clinical and Immunological Studies in the NONA Immune Cohort
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The oldest-old (people aged 80 or older) constituted 5 % of the population in Sweden in 2000, an increase from 1.5 % fifty years earlier. The immune system undergoes dramatic changes at high age, sometimes referred to as “immunosenescence”. However, the natures of these changes, and in particular, their clinical consequences are incompletely understood. In a previous longitudinal study, a set of immune parameters were identified and termed immune risk phenotype (IRP) because of an association with increased mortality. The IRP consists of changes in the T lymphocyte compartment, in particular an inverted CD4/CD8 ratio. The IRP was found to be associated with cytomegalovirus (CMV) infection, which through expansions of cytolytic anti-viral CD8 cell responses was ascribed a role in the development of IRP. The general aim of this thesis was to increase the knowledge of changes in the immune system and their clinical consequences in the oldest-old. The population-based random sample of the longitudinal NONA-Immune Study (n = 138, mean age 90 years at baseline) was used for all investigations.In paper I, the effects on sample size of various exclusion protocols for immune studies of the elderly was examined. The commonly used SENIEUR protocol, selecting individuals representing ‘normal ageing’, excluded 90 % of nonagenarians. Based on different protocol criteria, individuals were grouped into ‘very healthy’, ‘moderately healthy’ or ‘frail’. The prevalence of CMV was similar across the groups. Further, differentiated CD8 populations associated with CMV, i.e. those expressing CD56, CD57 and CD45RA while lacking expression of CD27 and CD28, were equally distributed across the groups of the oldest-old, but were, as expected, significantly increased in the elderly compared to a middle aged control group. The findings showed that lymphocyte subsets associated with IRP might serve as significant biomarkers of ageing independent of the overall health status, also supporting the notion that immunological studies of the oldest-old should be done in population-based non-selected populations.The IRP and the presence of low-grade inflammation, for example increase of IL-6 in plasma, constitute major predictors of 2-year mortality in the oldest-old. In paper II, the CD4/CD8 ratio and IL-6 were found to predict 97 % of observed survival and 57 % of deaths over 2 years. The impact of IRP and IL-6 on 2-year survival was independent of age, sex and several diseases. The longitudinal design allowed temporal evaluations, suggesting a sequence of events starting with IRP and leading to inflammation in the decline state. Four-year mortality in the oldest-old (paper III) was found to be mainly related to markers of inflammation and IRP. Individuals with both inverted CD4/CD8 ratio and high IL-6 level had significantly higher 4 year mortality (82 %) compared to individuals with CD4/CD8 ratio ³ 1 and low IL-6 level (29 %) at baseline. The presence of IRP and increased IL-6 level showed some associations with presence of diseases; in particular, IL6 was associated with the presence of cognitive impairment. However, despite being strong predictors of mortality, IRP and IL-6 could not be linked to any specific cause of death, probably due to the multi-factorial nature of these factors. The prevalence of antinuclear antibodies (ANA) in the oldest-old was higher compared to younger controls (paper IV). The difference across age was most pronounced in men, showing low levels at younger age, whereas the prevalence among the oldest-old men reached a similar level as in women. There was no association between the presence of ANA and IRP, CMV status or health status in the oldest-old.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Wikby, Anders, et al.
(författare)
-
An immune risk phenotype, cognitive impairment, and survival in very late life : Impact of allostatic load in Swedish octogenarian and nonagenarian humans
- 2005
-
Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X. ; 60:5, s. 556-565
-
Tidskriftsartikel (refereegranskat)abstract
- In the previous OCTO longitudinal study, we identified an immune risk phenotype (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 examine 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 measurements consisted of determinations of T-cell subsets, plasma interleukin 6 and cytomegalovirus 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), decreased 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 follow-up, indicating an allostatic overload. Copyright 2005 by The Gerontological Society of America.
|
|
