Differential Expression of CD45RO and CD45RA in Bovine T Cells

Kandel, Anmol; Li, Lei; Hada, Akanksha; Xiao, Zhengguo

doi:10.3390/cells11111844

Cited by 5 publications

(23 citation statements)

References 84 publications

(156 reference statements)

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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%

“…Although how CD45RO is spliced in cattle is unknown, a protein of a molecular weight similar to that in humans (i.e., 180 kDa) was precipitated (Bembridge et al 1995), using the most popular monoclonal antibody clone IL-A116 (Bembridge et al 1995;Ballingall et al 2001;Endsley et al 2006;Denis et al 2011;Hogg et al 2011;Blunt et al 2015;Maggioli et al 2015;Frie et al 2017;Elnaggar et al 2021;Jonsson et al 2021;Mitoma et al 2021). Similarly, there are ten monoclonal antibodies that recognize the high molecular weight isoform in cattle (Dutia et al 1993, Howard andNaessens 1993); among them, clones CC76 and GC6A have already been applied to detect the bovine homologue of CD45RA (Endsley et al 2007;Denis et al 2011;Kandel et al 2022).…”

Section: Alternative Splicing Generates Cd45ra/ro In Humansmentioning

confidence: 99%

“…In this regard, human research has utilized multiple markers besides CD45RA/ RO (Wills et al 1999;Gattinoni et al 2011;Mahnke et al 2013;Jung et al 2021); for example, several proteins including CD127, CD27, CD95, CD11a, CD18 and CD28 have been included in the evaluation of human memory CD8 + T cells (Hamann et al 1997, Samji and Khanna 2017, Martin and Badovinac 2018. Nonetheless, bovine memory T cells are commonly detected using CD45RO + /CD45RA -, despite conflicting evidence Guerra-Maupome et al 2019;Kandel et al 2022). Recently, we sought to validate CD45RO + / CD45RAas markers for memory T cells in cattle using the conventional cytokine induction assay (Kandel et al 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Nonetheless, bovine memory T cells are commonly detected using CD45RO + /CD45RA -, despite conflicting evidence Guerra-Maupome et al 2019;Kandel et al 2022). Recently, we sought to validate CD45RO + / CD45RAas markers for memory T cells in cattle using the conventional cytokine induction assay (Kandel et al 2022). A weak correlation between CD45RA/RO expression and memory T cells in cattle was revealed (Kandel et al 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we sought to validate CD45RO + / CD45RAas markers for memory T cells in cattle using the conventional cytokine induction assay (Kandel et al 2022). A weak correlation between CD45RA/RO expression and memory T cells in cattle was revealed (Kandel et al 2022). In this review, we examined the current literature, and discussed some of our findings to assess the reliability of CD45RO + /CD45RAas authentic markers for memory T cells in cattle.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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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Section: Alternative Splicing Generates Cd45ra/ro In Humansmentioning

confidence: 99%

Section: Alternative Splicing Generates Cd45ra/ro In Humansmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

2022

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Characterization of T-cell subsets in response to foot-and-mouth disease bivalent inactivated vaccine in Chinese Holstein cows

Zhang,

Wang,

Yao

et al. 2023

Microbiol Spectr

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Traditional vaccine efficacy evaluation predominantly relies on antibody levels, while the assessment of T-cell responses remains underexplored. In this study, we employed multi-parameter flow cytometry to comprehensively analyze T-cell responses in cows vaccinated against foot-and-mouth disease (FMD). We categorized the cows into high and low vaccine potency groups based on antibody levels and investigated differences in T-cell responses between these groups. Phenotypic analysis revealed a significant reduction in CD4, CD8, and γδ T cells in peripheral blood following FMD vaccine inoculation, concomitant with altered CD44 expression. Intriguingly, FMD vaccination induced a marked increase in the percentage of CD4 + CD8 + double-positive (DP) T cells in cow peripheral blood. Notably, cows with high vaccine potency exhibited a significantly higher proportion of CD4 + CD8 + DP T cells compared to those with low potency post-vaccination, suggesting their potential involvement in FMD vaccine-induced immune protection, possibly through the regulation of B-cell antibody secretion. Additionally, FMD vaccination led to the generation of central memory CD4 and CD8 T cells but not γδ T cells. Our groundbreaking findings shed light on the latent function of CD4 + CD8 + DP T cells in FMD vaccine-induced immune protection and established a novel method for evaluating FMD vaccine efficacy based on T-cell responses. IMPORTANCE Vaccination plays a crucial role in the prevention and control of FMD; however, outbreaks persist occurring worldwide. Assessing the immune response to FMD vaccines is essential for effective prevention of FMD. In this study, a seven-color flow cytometry protocol was developed to systematically evaluate the T-cell response of Chinese Holstein cows vaccinated with FMD bivalent inactivated vaccine. Our findings showed that while most T-cell subsets (%) decreased post-vaccination, a significant increase was observed in CD4 + CD8 + DP T cells, which was consistent with the levels of specific foot-and-mouth disease virus (FMDV) antibodies. These findings suggested that CD4 + CD8 + DP T cells could serve as a potential biomarker for the evaluation of cellular and humoral responses to FMDV vaccination. Additionally, we should be aware of the potential decline in cellular immunity among cattle during FMD vaccination, as this may increase the risk of other pathogen-related issues.

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Differentiation and Regulation of Bovine Th2 Cells In Vitro

Kandel,

Li,

Wang

et al. 2024

Cells

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Bovine Th2 cells have usually been characterized by IL4 mRNA expression, but it is unclear whether their IL4 protein expression corresponds to transcription. We found that grass-fed healthy beef cattle, which had been regularly exposed to parasites on the grass, had a low frequency of IL4+ Th2 cells during flow cytometry, similar to animals grown in feedlots. To assess the distribution of IL4+ CD4+ T cells across tissues, samples from the blood, spleen, abomasal (draining), and inguinal lymph nodes were examined, which revealed limited IL4 protein detection in the CD4+ T cells across the examined tissues. To determine if bovine CD4+ T cells may develop into Th2 cells, naïve cells were stimulated with anti-bovine CD3 under a Th2 differentiation kit in vitro. The cells produced primarily IFNγ proteins, with only a small fraction (<10%) co-expressing IL4 proteins. Quantitative PCR confirmed elevated IFNγ transcription but no significant change in IL4 transcription. Surprisingly, GATA3, the master regulator of IL4, was highest in naïve CD4+ T cells but was considerably reduced following differentiation. To determine if the differentiated cells were true Th2 cells, an unbiased proteomic assay was carried out. The assay identified 4212 proteins, 422 of which were differently expressed compared to those in naïve cells. Based on these differential proteins, Th2-related upstream components were predicted, including CD3, CD28, IL4, and IL33, demonstrating typical Th2 differentiation. To boost IL4 expression, T cell receptor (TCR) stimulation strength was reduced by lowering anti-CD3 concentrations. Consequently, weak TCR stimulation essentially abolished Th2 expansion and survival. In addition, extra recombinant bovine IL4 (rbIL4) was added during Th2 differentiation, but, despite enhanced expansion, the IL4 level remained unaltered. These findings suggest that, while bovine CD4+ T cells can respond to Th2 differentiation stimuli, the bovine IL4 pathway is not regulated in the same way as in mice and humans. Furthermore, Ostertagia ostertagi (OO) extract, a gastrointestinal nematode in cattle, inhibited signaling via CD3, CD28, IL4, and TLRs/MYD88, indicating that external pathogens can influence bovine Th2 differentiation. In conclusion, though bovine CD4+ T cells can respond to IL4-driven differentiation, IL4 expression is not a defining feature of differentiated bovine Th2 cells.

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Differential Expression of CD45RO and CD45RA in Bovine T Cells

Cited by 5 publications

References 84 publications

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

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

Characterization of T-cell subsets in response to foot-and-mouth disease bivalent inactivated vaccine in Chinese Holstein cows

Differentiation and Regulation of Bovine Th2 Cells In Vitro

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