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Biology subjects

Allore, H. G.

Publications and source records attributed to Allore, H. G..

3 recordsLinked to original sources

Altered CD8+ T cell associated aging gene signature in the peripheral blood of patients with Alzheimer's disease.

INTRODUCTIONEffector memory (EM) CD8+ T cells have been associated with poor cognition in Alzheimers disease (AD). Our lab recently discovered an age-associated gene expression signature of IL-7 receptor alpha (IL-7R)low EM CD8+ T cells. We hypothesized that individuals with AD have altered levels of this IL-7Rlow aging gene expression. METHODSForty genes associated with IL-7Rlow EM CD8+ T cells, AD, or memory, were analyzed in peripheral blood of participants with normal cognition, mild cognitive impairment, and dementia by qPCR. RESULTSOf the eight genes that were found to be differentially expressed based on clinical diagnosis, 5 genes (62.5%) were IL-7Rlow aging genes. Principal component analysis revealed 3 clusters of participants with dementia which had distinct expression levels of IL-7Rlow aging genes and cognitive function. DISCUSSIONOur findings support the possible relationship of the IL-7Rlow EM CD8+ T cell aging signature with cognition in individuals with dementia due to AD.

immunology↗

Platelet response to influenza vaccination reflects effects of aging

Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity, but how age and alterations in functional status such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome in younger (age 21-35) and older (age [≥] 65) adults (including frail and non-frail individuals) following influenza vaccination. Prior to vaccination, we identified an age- and frailty-associated increase in expression of platelet activation and mitochondrial RNAs and decrease in RNAs encoding proteins mediating translation. Using tensor decomposition analysis, we also elucidated dynamic post-vaccination platelet activation and translation signatures associated with age and frailty. At the protein level, enhanced platelet activation was found in non-frail older adults, compared to young individuals both prior to and post-vaccine; but frail adults showed decreased platelet activation compared to non-frail that could reflect the influence of decreased translation RNA expression. Our results reveal an age-dependent alteration in platelet function prior to and post-vaccination that may contribute to age-associated chronic inflammation.

immunology↗

Viral shedding and transmission after natural infection and vaccination in an animal model of SARS-CoV-2 propagation

At present, global immunity to SARS-CoV-2 resides within a heterogeneous combination of susceptible, naturally infected and vaccinated individuals. The extent to which viral shedding and transmission occurs on re-exposure to SARS-CoV-2 after prior natural exposure or vaccination is an emerging area of understanding. We used Sialodacryoadenitis Virus (SDAV) in rats to model the extent to which immune protection afforded by prior natural infection via high risk (inoculation; direct contact) or low risk (fomite) exposure, or by vaccination, influenced viral shedding and transmission on re-exposure. On initial infection, we confirmed that amount, duration and consistency of viral shedding were correlated with exposure risk. Animals were reinfected after 3.7-5.5 months using the same exposure paradigm. Amount and duration of viral shedding were correlated with re-exposure type and serologic status. 59% of seropositive animals shed virus. Previously exposed seropositive reinfected animals were able to transmit virus to 25% of naive recipient rats after 24-hour exposure by direct contact. Rats vaccinated intranasally with a related virus (Parkers Rat Coronavirus) were able to transmit SDAV to only 4.7% of naive animals after a 7-day direct contact exposure, despite comparable viral shedding. Observed cycle threshold values associated with transmission in both groups ranged from 29-36 cycles, however observed shedding was not a prerequisite for transmission. Results indicate that low-level shedding in both naturally infected and vaccinated seropositive animals can propagate infection in susceptible individuals. Extrapolated to COVID-19, our results suggest that continued propagation of SARS-CoV-2 by seropositive previously infected or vaccinated individuals is possible.

microbiology↗