CD4+ CD44v.low cells are unique peripheral precursors that are distinct from recent thymic emigrants and stem cell-like memory cells

Zhao, Chunfang; Marrero, Idania; Narsale, Aditi; Moya, R.R. Martínez; Davies, Joanna D.

doi:10.1016/j.cellimm.2015.04.002

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…Previously published work from our group has shown that injecting CD4 + precursor T cells into mice with cancer can both re‐establish balanced numbers of naïve, memory, and regulatory T cells and protect from muscle wasting . To our knowledge, these data were the first to show a link between muscle health and T cell homeostasis in mice.…”

Section: Introductionsupporting

confidence: 52%

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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Section: Introductionsupporting

confidence: 52%

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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“…Also both strains had an increase in CD62L high CD44 very low cells. This subset is reported to be enriched for naïve CD4 T cells with stem cell-like properties 27 . We checked the responsiveness of DN thymocytes to CXCL12 and CCL19 and mature SP CD4 thymocytes to the same chemokines and to S1P.…”

Section: Resultsmentioning

confidence: 99%

Loss of Gαi proteins impairs thymocyte development, disrupts T-cell trafficking, and leads to an expanded population of splenic CD4+PD-1+CXCR5+/− T-cells

Hwang

Harrison

Park

et al. 2017

Sci Rep

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Thymocyte and T cell trafficking relies on signals initiated by G-protein coupled receptors. To address the importance of the G-proteins Gαi2 and Gαi3 in thymocyte and T cell function, we developed several mouse models. Gαi2 deficiency in hematopoietic progenitors led to a small thymus, a double negative (DN)1/DN2 thymocyte transition block, and an accumulation of mature single positive (SP) thymocytes. Loss at the double positive (DP) stage of thymocyte development caused an increase in mature cells within the thymus. In both models an abnormal distribution of memory and naïve CD4 T cells occurred, and peripheral CD4 and CD8 T cells had reduced chemoattractant responses. The loss of Gαi3 had no discernable impact, however the lack of both G-proteins commencing at the DP stage caused a severe T cell phenotype. These mice lacked a thymic medullary region, exhibited thymocyte retention, had a peripheral T cell deficiency, and lacked T cell chemoattractant responses. Yet a noteworthy population of CD4+PD-1+CXCR5+/− cells resided in the spleen of these mice likely due to a loss of regulatory T cell function. Our results delineate a role for Gαi2 in early thymocyte development and for Gαi2/3 in multiple aspects of T cell biology.

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“…Cell subsets with a Th2 bias have been noted previously and include recent thymic emigrants (RTE) [34] and CD4 + CD44 v.low peripheral precursor cells [35]. We have ruled out the possibility that CD25 + CD127 hi cells are either RTE or CD44 v.low precursor cells because they do not express the naïve cell marker, CD45RA.…”

Section: Discussionmentioning

confidence: 96%

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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CD4+ CD44v.low cells are unique peripheral precursors that are distinct from recent thymic emigrants and stem cell-like memory cells

Cited by 4 publications

References 36 publications

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

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

Loss of Gαi proteins impairs thymocyte development, disrupts T-cell trafficking, and leads to an expanded population of splenic CD4+PD-1+CXCR5+/− T-cells

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

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