Biomedical subjects

Anders Wikby

Publications and source records attributed to Anders Wikby.

22 records · Page 2Linked to original sources

PubMedDate not supplied

Mitochondrial DNA damage in lymphocytes: a role in immunosenescence?

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 mtDNA(4977) 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 mtDNA(4977) 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 mtDNA(4977) 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.

Adult↗

PubMedDate not supplied

Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study.

Results from a previous longitudinal study, the Swedish OCTO-Immune study, indicated that the combination of higher CD8 peripheral blood lymphocytes (PBLs), decreased CD4 PBLs, and poor proliferative response to mitogenic stimulation in very old humans were associated with an increased 2 year mortality. In follow up studies this combination of immune parameters was significantly associated with a CD4/CD8 ratio less than one and positive IgG serologic titers to cytomegalovirus (CMV). The present study, the Swedish NONA-Immune study, was an extension of that study, using a new sample of the very old. The results of this study confirmed the results of the previous study and extended the surface marker profile of the PBLs, indicating that the CD4/CD8 ratio change is associated with increased CD8 cells, decreased CD4 cells, and lymphocyte activation. The predominant phenotypes of the CD3+CD8+ cells were CD27-, CD28-, CD56+, and CD57+, CD45RA+, and double marked CD45RA+RO+. As in the OCTO study, the NONA-Immune data indicated that the changes are associated significantly with seropositive responses to CMV.

Adult↗

PubMedDate not supplied

Nonagenarians from the Swedish NONA Immune Study have increased plasma antioxidant capacity and similar levels of DNA damage in peripheral blood mononuclear cells compared to younger control subjects.

The results of previous work from our laboratories have suggested that free radical damage to T cells as they age may contribute to the age-related decline in the T cell-mediated immune response. The aims of this investigation were to assess the efficiency of in vivo antioxidant capacity through determining the antioxidant capacity of plasma using the ferric reducing ability of plasma assay, and to assess the levels and types of DNA damage (as a measure of in vivo antioxidant efficiency) using the alkaline comet assay and two enzymatic modifications of the comet assay, in peripheral blood mononuclear cells (PBMCs) from nonagenarian subjects drawn from the Swedish NONA Immune Study. The results obtained were compared with those from middle-aged (40-60 years) controls to identify potential anti-immunosenescent effects of in vivo antioxidants. The results revealed a significantly higher plasma antioxidant capacity in NONA subjects compared to controls, and these results support a relationship between longevity and intact immune function, which may be underpinned by antioxidant defences which reduce free radical damage to PBMC, thus helping to maintain cell function. The NONA subjects were found to have similar levels of DNA damage in their PBMCs to those found in middle aged controls.

Adult↗

PubMedDate not supplied

Compromised interferon gamma (IFN-gamma) production in the elderly to both acute and latent viral antigen stimulation: contribution to the immune risk phenotype?

The elderly suffer from an increased incidence of infectious disease, accompanied by increased morbidity and mortality. Interferon-gamma plays an important role in defense against intracellular pathogens such as mycobacteria and viruses. A reduced capacity to produce this cytokine in the elderly, as demonstrated by our findings of significant decreases in IFN-gamma production in vitro on stimulation with bacterial products (LPS) or viral antigens (influenza vaccine), might therefore contribute to disease susceptibility. Moreover, accumulating data suggest that persistent infection with EBV and particularly CMV impacts upon the immune system in aging and may contribute to the immune risk phenotype (IRP), which predicts remaining longevity in the very elderly. Using tetramer technology and IFN-gamma ELISPOT assays, we found that the commonly-observed clonal expansions of CD8+ T-cells in the elderly were for the most part poorly-functional CMV- and EBV-specific cells, expressing little CD28. The resulting accumulation of dysfunctional cells may lead to a reduction of the repertoire of functional T-cells available for responses to novel antigens. Further longitudinal studies are needed to demonstrate whether cytokines such as IFN-g are also part of the IRP. Improving the definition of the IRP will help to understand and thus prevent or reverse age-associated immune dysfunction.

Aged↗