Allelic Variation in Protein Tyrosine Phosphatase Receptor Type-C in Cattle Influences Erythrocyte, Leukocyte and Humoral Responses to Infestation With the Cattle Tick Rhipicephalus australis

Jonsson, N.N.; Cox, David K.; Piper, E.K.; Valdivieso, Emily F. Mantilla; Constantinoiu, Constantin; Jackson, Louise A.; Stear, M. J.; Ross, Elizabeth M.; Lew-Tabor, A.E.

doi:10.3389/fimmu.2021.675979

Cited by 5 publications

(6 citation statements)

References 28 publications

(46 reference statements)

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“…Microglia migration is decreased in Dock10 −/− mice ( Namekata et al, 2020 ). Ptprc encodes protein tyrosine phosphatase receptor type C or CD45, which affects cell adhesion, migration, cytokine signaling, cell development, and activation state ( Jonsson et al, 2021 ). Tbc1d2 (or Armus) encodes a GTPase-activating protein for RAB7A GTPase.…”

Section: Resultsmentioning

confidence: 99%

Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer’s Disease

et al. 2022

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A small dose of the anti-HIV drug efavirenz (EFV) was previously discovered to activate CYP46A1, a cholesterol-eliminating enzyme in the brain, and mitigate some of the manifestation of Alzheimer’s disease in 5XFAD mice. Herein, we investigated the retina of these animals, which were found to have genetically determined retinal vascular lesions associated with deposits within the retinal pigment epithelium and subretinal space. We established that EFV treatment activated CYP46A1 in the retina, enhanced retinal cholesterol turnover, and diminished the lesion frequency >5-fold. In addition, the treatment mitigated fluorescein leakage from the aberrant blood vessels, deposit size, activation of retinal macrophages/microglia, and focal accumulations of amyloid β plaques, unesterified cholesterol, and Oil Red O-positive lipids. Studies of retinal transcriptomics and proteomics identified biological processes enriched with differentially expressed genes and proteins. We discuss the mechanisms of the beneficial EFV effects on the retinal phenotype of 5XFAD mice. As EFV is an FDA-approved drug, and we already tested the safety of small-dose EFV in patients with Alzheimer’s disease, our data support further clinical investigation of this drug in subjects with retinal vascular lesions or neovascular age-related macular degeneration.

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Section: Resultsmentioning

confidence: 99%

Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer’s Disease

et al. 2022

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“…In humans, CD45 is expressed in a combination of multiple isoforms generated through alternative splicing of the CD45 pre-mRNA at exons 4, 5, and 6 [ 26 , 28 , 29 ]. Inclusion and exclusion of these three exons differentially generate CD45 isoforms, such as the high molecular weight CD45RA and the low molecular weight CD45RO [ 26 , 30 ]. Specifically, the shortest CD45RO transcript is generated through the exclusion of exons (4, 5, and 6) while still retaining 3 and 7, which are shared by all the other isoforms [ 26 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…Inclusion and exclusion of these three exons differentially generate CD45 isoforms, such as the high molecular weight CD45RA and the low molecular weight CD45RO [ 26 , 30 ]. Specifically, the shortest CD45RO transcript is generated through the exclusion of exons (4, 5, and 6) while still retaining 3 and 7, which are shared by all the other isoforms [ 26 , 30 ]. Therefore, selective detection of CD45RO transcript by quantitative PCR (qPCR) is not practical.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, selective detection of CD45RO transcript by quantitative PCR (qPCR) is not practical. Instead, due to the highly conserved nature of CD45 protein across the mammalian species [ 28 , 31 ], bovine CD45RO expression is commonly examined at the protein level using a monoclonal antibody (clone # ILA116) in flow cytometry [ 5 , 8 , 24 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Bembridge et al (1995) in their seminal research first used this monoclonal antibody (clone #ILA116) to precipitate bovine CD45RO, which had a molecular weight very close to that of humans (180 kDa), and suggested that this isoform could be associated with memory [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Differential Expression of CD45RO and CD45RA in Bovine T Cells

Kandel¹,

Li²,

Hada³

et al. 2022

Cells

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Effective vaccination induces immune memory to protect animals upon pathogen re-encounter. Despite contradictory reports, bovine memory T cells are identified based on two isoforms of CD45, expression of CD45RO plus exclusion of CD45RA. In this report, we contrasted CD45RA/RO expression on circulatory T cells with IFNγ and IL4 expression induced by a conventional method. To our surprise, 20% of cattle from an enclosed herd did not express CD45RO on T cells without any significant difference on CD45RA expression and IFNγ or IL4 induction. In CD45RO expressing cattle, CD45RA and CD45RO expressions excluded each other, with dominant CD45RO (>90%) expression on gamma delta (γδ) followed by CD4+ (60%) but significantly higher CD45RA expression on CD8+ T cells (about 80%). Importantly, more than 80% of CD45RO expressing CD4+ and CD8+ T cells failed to produce IFNγ and IL-4; however, within the cytokine inducing cells, CD4+ T cells highly expressed CD45RO but those within CD8+ T cells mostly expressed CD45RA. Hence, CD45RO is not ubiquitously expressed in cattle, and rather than with memory phenotype, CD45RA/RO expression are more associated with distinct T cell subtypes.

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“…1. Unfortunately, the information on CD45 splicing has not been explored in cattle, but genetic analysis suggests that at least six CD45 isoforms may exist, of which, some have already been detected at the protein level using antibodies (Bembridge et al 1995;Guerra-Maupome et al 2019;Jonsson et al 2021;Kandel et al 2022).…”

Section: Alternative Splicing Generates Cd45ra/ro In Humansmentioning

confidence: 99%

Are CD45RO+ and CD45RA- genuine markers for bovine memory T cells?

2022

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Effective vaccination induces memory T cells, which protect the host against pathogen re-infections. Therefore, detection of memory T cells is essential for evaluating vaccine efficacy, which was originally dependent on cytokine induction assays. Currently, two isoforms of CD45 tyrosine phosphatase, CD45RO expression and CD45RA exclusion (CD45RO+/ CD45RA-) are used extensively for detecting memory T cells in cattle. The CD45RO+/CD45RA- markers were first established in humans around three decades ago, and were adopted in cattle soon after. However, in the last two decades, some published data in humans have challenged the initial paradigm, and required multiple markers for identifying memory T cells. On the contrary, memory T cell detection in cattle still mostly relies on CD45RO+/CD45RA- despite some controversial evidence. In this review, we summarized the current literature to examine if CD45RO+/CD45RA- are valid markers for detecting memory T cells in cattle. It seems CD45RA and CD45RO (CD45RA/RO) as markers for identifying bovine memory T cells are questionable.

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Allelic Variation in Protein Tyrosine Phosphatase Receptor Type-C in Cattle Influences Erythrocyte, Leukocyte and Humoral Responses to Infestation With the Cattle Tick Rhipicephalus australis

Cited by 5 publications

References 28 publications

Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer’s Disease

Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer’s Disease

Differential Expression of CD45RO and CD45RA in Bovine T Cells

Are CD45RO+ and CD45RA- genuine markers for bovine memory T cells?

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