| 1. |
- Bengnér, Malin, et al.
(författare)
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Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity.
- 2014
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Ingår i: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:2, s. 571-582
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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.
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| 2. |
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| 3. |
- Nilsson, Bengt-Olof, 1954-, et al.
(författare)
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The Immune Risk Phenotype and IL-6 among Nonagenarians and Associations with Morbidity and Mortality : Findings from the Swedish NONA Immune Longitudinal Study
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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.
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| 4. |
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| 5. |
- Strindhall, Jan, et al.
(författare)
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Humoral response to influenza vaccination in relation to pre-vaccination antibody titres, vaccination history, cytomegalovirus serostatus and CD4/CD8 ratio
- 2016
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Ingår i: INFECTIOUS DISEASES. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 48:6, s. 436-442
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Tidskriftsartikel (refereegranskat)abstract
- Background Annual vaccination against influenza virus is generally recommended to elderly and chronically ill, but the relative importance of factors influencing the outcome is not fully understood. Methods In this study of 88 individuals all aged 69 years, the increase in haemagglutinin-inhibiting (HI) antibodies to trivalent inactivated influenza vaccine was correlated with HI titres before vaccination, prior vaccinations against influenza, cytomegalovirus serostatus and, as an estimate of immune risk profile, the ratio between CD4 + and CD8 + T cells. Results Vaccine responses were impaired by high pre-existing HI antibody titres. For influenza B repeated vaccinations and an inverse CD4/CD8 ratio had a negative impact on the vaccine response. Cytomegalovirus seropositivity had no apparent effect on HI titres before or after vaccination. Conclusions It is concluded that both pre-existing HI antibodies and previous vaccinations to influenza may influence the humoral response to influenza vaccination and that a CD4/CD8 ratio < 1 may indicate an impaired ability to respond to repeated antigenic stimulation.
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| 6. |
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| 7. |
- Strindhall, Jan, et al.
(författare)
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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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Ingår i: Age (Omaha). - : Springer Netherlands. - 0161-9152 .- 1574-4647. ; 35:3, s. 985-991
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Wikby, Anders, et al.
(författare)
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An immune risk phenotype, cognitive impairment, and survival in very late life : Impact of allostatic load in Swedish octogenarian and nonagenarian humans
- 2005
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1079-5006 .- 1758-535X. ; 60:5, s. 556-565
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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.
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