A pilot study showing associations between frequency of CD4+ memory cell subsets at diagnosis and duration of partial remission in type 1 diabetes

Moya, R.R. Martínez; Robertson, Hannah Kathryn; Payne, Dawson; Narsale, Aditi; Koziol, Jim; Davies, Joanna D.

doi:10.1016/j.clim.2016.04.012

Cited by 25 publications

(31 citation statements)

References 53 publications

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“…This study was designed to further characterize CD4 + CD25 + CD127 hi cells, a non-Treg subset of memory T cells that we have previously shown to correlate with the rate of disease progression in children newly diagnosed with T1D, with a higher frequency of cells correlating with slower rate of disease progression [18,19]. Our new data show that CD25 + CD127 hi cells are present in healthy people at a relative frequency similar to that in T1D patients with the slowest rate of disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…CD25 + CD127 hi cells also express a high surface density of CD44 and the CD44 variant CD44v6 [18], receptors for hyaluronan (HA), signaling through which inhibits apoptosis [52–54]. Moreover, CD44 co-stimulation induces CD25 expression and signaling in the presence of low levels of circulating IL-2 [55].…”

Section: Discussionmentioning

confidence: 99%

“…We have identified a population of CD4 + memory T cells by their co-expression of CD25, the high affinity IL-2 receptor, and a high density of CD127, the IL-7 receptor [18,19]. In children newly diagnosed with type 1 diabetes (T1D) these cells are significantly associated with the length of partial remission, measured using insulin dose adjusted glycated hemoglobin (HbA1c) levels (IDAA1c), with an increase in frequency associated with protection.…”

Section: Introductionmentioning

confidence: 99%

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Human CD4+ CD25+ CD127hi cells and the Th1/Th2 phenotype

Narsale

Moya

Davies

2018

Clinical Immunology

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CD4 T cells that co-express CD25 and CD127 (CD25CD127) make up around 20% of all circulating CD4 memory T cells in healthy people. The clinical significance of these cells is that in children with type 1 diabetes their relative frequency at diagnosis is significantly and directly correlated with rate of disease progression. The purpose of this study was to further characterize the CD25CD127 cells. We show that they are a mix of Th1 and Th2 cells however, they have a significantly higher relative frequency of pre-committed and committed Th2 cells, and secrete significantly higher levels of Th2-type cytokines than CD25 memory T cells. Further, these cells are neither exhausted nor senescent and proliferate to the same extent as CD25 memory cells. Thus, CD25CD127 cells are a highly active subset of memory T cells that might play a role in controlling inflammation via anti-inflammatory Th2-type deviation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human CD4+ CD25+ CD127hi cells and the Th1/Th2 phenotype

Narsale

Moya

Davies

2018

Clinical Immunology

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“…Regulatory cells (Treg) were identified by their high expression of CD25 and low expression of CD127 as described previously using the BD Biosciences Treg cocktail that includes antibodies specific for CD4, CD127, and CD25 with CD3. CD25 + CD127 hi cells were also identified using the BD Biosciences Treg cocktail as CD3 + CD4 + CD25 + CD127 hi . Activated Treg were identified as CD3 + CD4 + CD45RA − Foxp3 hi .…”

Section: Methodsmentioning

confidence: 99%

Cancer‐driven changes link T cell frequency to muscle strength in people with cancer: a pilot study

Narsale

Moya

et al. 2019

J cachexia sarcopenia muscle

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Background Tumour growth can promote the loss of muscle mass and function. This is particularly disturbing because overall survival is significantly reduced in people with weaker and smaller skeletal muscle. The risk of cancer is also greater in people who are immune deficient. Muscle wasting in mice with cancer can be inhibited by infusion of CD4 + precursor T cells that restore balanced ratios of naïve, memory, and regulatory T cells. These data are consistent with the hypothesis that stronger anti‐cancer T cell immunity leads to improved muscle mass and function. As a first step to testing this hypothesis, we determined whether levels of circulating T cell subsets correlate with levels of muscle strength in people with cancer. Methods The frequency of circulating CD4 + and CD8 + naïve, memory, and regulatory T cell subsets was quantified in 11 men with gastrointestinal cancer (aged 59.3 ± 10.1 years) and nine men without cancer (aged 60 ± 13 years), using flow cytometry. T cell marker expression was determined using real‐time PCR and western blot analyses in whole blood and peripheral blood mononuclear cells. Handgrip strength, one‐repetition maximum chest press, and knee extension tests were used to determine muscle strength. Performance was determined using a stair climb test. Body composition was determined using dual‐energy X‐ray absorptiometry scan. The Karnofsky and ECOG scales were used to assess functional impairment. Correlations between frequencies of cell subsets with strength, performance, and body composition were determined using regression analyses. Results Our data show significant correlations between (i) higher frequencies of CD8 + naïve ( P = 0.02) and effector memory ( P = 0.003) T cells and lower frequencies of CD8 + central memory T cells ( P = 0.002) with stronger handgrip strength, (ii) lower frequency of regulatory cells with greater lean mass index ( P = 0.04), (iii) lower frequency of CD8 + T cells that express CD95 with greater stair climb power ( P = 0.003), (iv) higher frequency of T cells that co‐express CD197 and CD45RA and greater one‐repetition maximum knee extension strength ( P = 0.008), and (iv) higher expression of CD4 in whole blood with greater functional impairment ( P = 0.004) in people with cancer. Conclusions We have identified significant correlations between levels of T cell populations and muscle strength, performance, and body composition in people with cancer. These data justify a follow‐up study with a larger cohort to test the validity of the findings.

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“…Moreover, low serum IFN-γ concentrations at T1D clinical onset provide a strong positive predictive value for partial remission [42]. The role of immunoregulatory factors in the honeymoon phase can also be observed by an alteration in the frequency of T-cell subsets in peripheral blood: CD4 + CD45R0 + memory T cells, activated T-regulatory lymphocytes, and CD4 + CD25 + CD127 high (indirectly associated with immunoregulation) [43]. These changes are strongly associated with partial remission duration, glucose control, and β-cell tolerance and function.…”

Section: Collateral Damage Of the T1d Remission Phase And Newly Propomentioning

confidence: 99%

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

Fonolleda¹,

Murillo²,

Vázquez

et al. 2017

Horm Res Paediatr

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Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the β-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of β-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called “honeymoon phase,” which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining β-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to β-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.

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A pilot study showing associations between frequency of CD4+ memory cell subsets at diagnosis and duration of partial remission in type 1 diabetes

Cited by 25 publications

References 53 publications

Human CD4+ CD25+ CD127hi cells and the Th1/Th2 phenotype

Human CD4+ CD25+ CD127hi cells and the Th1/Th2 phenotype

Cancer‐driven changes link T cell frequency to muscle strength in people with cancer: a pilot study

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

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