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Age-associated alterations in ?? T-cells are present predominantly in individuals infected with Cytomegalovirus.

ABSTRACT: BACKGROUND:Despite the common perception that latent Cytomegalovirus (CMV) infection is usually symptom-free, emerging epidemiological evidence suggests that it may in fact be associated with higher mortality over extended follow-up. Mechanisms responsible for this potentially important effect are unclear. CMV infection is known to have a large impact on the distribution of T cell phenotypes, especially the accumulation of late-stage differentiated CD8+, as well as V?2- ?? T-cells, which are the main subset of ?? T-cells involved in anti-CMV immunity. Its impact on ?? T-cells in the aging context is less well-defined. RESULTS:Here, we investigated a group of healthy individuals aged between 21 and 89 years, in order to correlate the frequency and differentiation status of ?? T-cells with age. We found that these parameters were only marginally influenced by age, but were marked in people with a latent CMV infection. Thus, we observed a significant age-associated accumulation of late-differentiated T-cells within the V?2- population, but only in CMV-seropositive donors. There was also a strong trend towards reduced frequency of early-differentiated cells within the V?2- phenotype. Older people had significantly higher anti-CMV IgG titers, which in turn correlated significantly with a lower V?2+/V?2- ratio and a shift from early- to a late-differentiated V?2- T-cell phenotype. CONCLUSIONS:Our findings demonstrate a strong influence of CMV on ?? T-cells during human ageing, similar to that observed for ?? T-cells. Differences between donors of different ages are more marked in CMV-infected individuals. The biological implications of this potent age-associated CMV-mediated immune-modulation require clarification.

SUBMITTER: Wistuba-Hamprecht K

PROVIDER: S-EPMC3703274 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus.

Wistuba-Hamprecht Kilian K Frasca Daniela D Blomberg Bonnie B Pawelec Graham G Derhovanessian Evelyna E

Immunity & ageing : I & A 20130703 1

<h4>Background</h4>Despite the common perception that latent Cytomegalovirus (CMV) infection is usually symptom-free, emerging epidemiological evidence suggests that it may in fact be associated with higher mortality over extended follow-up. Mechanisms responsible for this potentially important effect are unclear. CMV infection is known to have a large impact on the distribution of T cell phenotypes, especially the accumulation of late-stage differentiated CD8+, as well as Vδ2- γδ T-cells, which ...[more]

PMID: 23822093

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Project description:PurposeIn adults with long-term HIV infection, low bone density and increased fracture risk have emerged as significant comorbidities. Our aim was to assess the association of exercise, nutrition, and medications with bone quality in adults with long-term HIV infection.MethodsForty-three adults with HIV infection were enrolled (median BMI 25.7, range 18.2-35.6 kg/m2; median age 57, range 50-69 years). Participants underwent ultradistal radius and tibia high-resolution peripheral quantitative CT (HR-pQCT). Questionnaires included the revised Community Healthy Activities Model Program for Seniors (CHAMPS), the Mini Nutritional Assessment (MNA) as well as medication assessments. Multivariable linear regression models were used to evaluate the association of exercise, nutritional status, tenofovir disoproxil fumarate (TDF) and protease inhibitor (PI) use with bone density and microstructure, adjusting for demographic risk factors.ResultsIn regression models, higher nutrition scores were associated with higher tibia cortical thickness (R2 = 0.23; β = 0.03; p = 0.044) and higher radius cortical BMD (R2 = 0.43; β = 8.4; p = 0.026). Higher weekly frequency of all physical activities was significantly associated with higher radius trabecular BMD (R2 = 0.38; β = 0.96; p = 0.050), higher radius trabecular number (R2 = 0.31; β = 0.01; p = 0.026), lower tibia and radius trabecular separation (tibia: R2 = 0.30; β = -0.003; p = 0.038; radius: R2 = 0.35; β = -0.003; p = 0.021), and higher radius bone stiffness (R2 = 0.45; β = 0.38; p = 0.047). Higher frequency of bone loading physical activities was significantly associated with higher tibia trabecular density (R2 = 0.44; β = 4.06; p = 0.036), higher tibia bone stiffness (R2 = 0.46; β = 3.06; p = 0.050), and higher tibia estimated failure load (R2 = 0.46; β = 0.17; p = 0.049). TDF used in combination with a PI was associated with lower radius trabecular BMD (R2 = 0.39; β = -41.2; p = 0.042), lower radius trabecular number (R2 = 0.34; β = -0.44; p = 0.009) and greater radius trabecular separation (R2 = 0.42; β = 0.16; p = 0.002), while TDF use without a PI was not associated with reduced bone quality.ConclusionsIn adults with HIV infection, malnutrition is associated with poor cortical bone quality, while reduced frequency of physical activities and specifically reduced frequency of mechanical loading activities are associated with deficient trabecular bone structure and reduced estimates of bone strength. TDF use in combination with a PI is associated with deleterious effects on trabecular bone structure.

Dataset Information

Age-associated alterations in ?? T-cells are present predominantly in individuals infected with Cytomegalovirus.

Publications

Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus.

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