Cachexia in the non‐obese diabetic mouse is associated with CD4<sup>+</sup> T‐cell lymphopenia

Zhao, Chunfang; Wang, Zhuanzhi; Robertson, Michael W.; Davies, Joanna D.

doi:10.1111/j.1365-2567.2008.02819.x

Cited by 10 publications

(24 citation statements)

References 66 publications

(88 reference statements)

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“…We have previously shown that CD44 v.low cells also express a high density of CD62L in addition to other markers for naïve phenotype cells [20] suggesting that they are a subset of the naïve CD4 + T cell compartment. As expected, all three markers are expressed at detectable levels on a subset of CD44 hi memory phenotype cells.…”

Section: Resultsmentioning

confidence: 99%

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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

Zhao

Marrero

Narsale

et al. 2015

Cellular Immunology

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CD4+ CD44v.low cells are peripheral precursor T cells that inhibit lymphopenia by generating a large CD4+ T cell pool containing balanced numbers of naïve, memory, and regulatory Foxp3+ cells with a diverse TCR repertoire. Recent thymic emigrants (RTE) and stem cell-like memory T cells (TSCM) can also replenish a T cell pool. In this study we formally test whether CD44v.low cells are the same population as RTE and TSCM. Our data show that, in contrast to RTE, CD44v.low cells express high levels of CD45RB and low levels of CD24. Moreover, CD44v.low cells isolated from mice devoid of RTE retain their capacity to repopulate lymphopenic mice with naïve and memory cells and Foxp3+ Tregs. In addition, CD44v.low cells do not express IL-2Rβ, Sca-1, and CXCR3, the phenotypic hallmarks of TSCM. Overall, these data demonstrate that CD44v.low cells are neither RTE nor TSCM.

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Section: Resultsmentioning

confidence: 99%

“…In addition to their similarity in expression of CXCR3, IL-2Rβ, Sca-1, and CD24 they both express a high density of CD45RB and CD62L, and a low density of CD44 [20]. There are also functional similarities between these two populations.…”

Section: Discussionmentioning

confidence: 99%

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

Zhao

Marrero

Narsale

et al. 2015

Cellular Immunology

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“…In addition, we have recently shown that a subset of CD4 + CD44 low cells, defined by their expression of the lowest density of CD44 (CD4 + CD44 v.low ), is depleted in diabetic mice at the onset of cachexia, but not in diabetic mice that are not cachexic (16). These data implicate the CD4 + CD44 v.low T cell subset as a hypothetical candidate for modulating the development of cachexia.…”

mentioning

confidence: 99%

“…Without insulin treatment, individuals with TID develop cachexia (5, 24). We have shown that wasting in the NOD mouse, the well-established mouse model for TID (25, 26), is also due to cachexia, with a dramatic loss of skeletal muscle weight, significant muscle protein loss, and activation of the ubiquitin protea-some pathway (16). In addition, muscle atrophy in the NOD mouse is associated with the presence of DNA fragmentation and a significant loss in muscle DNA content, suggesting the possibility that TID cachexia, like some models of cancer cachexia, involves apoptosis (27–29).…”

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confidence: 99%

A Novel Role for CD4+ T Cells in the Control of Cachexia

Wang

Zhao

Moya

et al. 2008

The Journal of Immunology

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Cachexia is the dramatic weight loss and muscle atrophy seen in chronic disease states, including autoimmunity, cancer, and infection, and is often associated with lymphopenia. We have previously shown that CD4+ T cells that express the lowest density of CD44 (CD4+CD44v.low) are significantly reduced in diabetic NOD mice that are cachexic compared with diabetic mice that are not cachexic. Using this model, and a model of cancer cachexia, we test the hypothesis that CD4+CD44v.low cells play an active role in protecting the host from cachexia. CD4+CD44v.low cells, but not CD4+ cells depleted of CD44v.low cells, delay the onset of wasting when infused into either diabetic or prediabetic NOD recipients. However, no significant effect on the severity of diabetes was detected. In a model of cancer cachexia, they significantly reduce muscle atrophy, and inhibit muscle protein loss and DNA loss, even when given after the onset of cachexia. Protection from wasting and muscle atrophy by CD4+CD44v.low cells is associated with protection from lymphopenia. These data suggest, for the first time, a role for an immune cell subset in protection from cachexia, and further suggest that the mechanism of protection is independent of protection from autoimmunity.

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“…These actions of insulin are largely mediated via the PI3K-mammalian target of rapamycin (mTOR) pathway (Fig. (2)) [48,[61][62][63][64][65][66]. Exercise can also activate the mTOR pathway, whereas amino acid supplementation, particularly leucine, promotes protein synthesis at the translational level to further mediate muscle growth and hypertrophy [43,63,67,68].…”

Section: Insulin Signalling and Skeletal Musclementioning

confidence: 99%

Skeletal Muscle Metabolism in the Pathology and Treatment of Type 1 Diabetes

Mann

Ayuso²,

Anguela³

et al. 2010

CPD

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Type 1 diabetes is characterised by the absence of circulating insulin due to the autoimmune destruction of beta-cells in the pancreas. Patients are traditionally treated with multiple daily injections of exogenous insulin analogues. However, although these therapies improve quality of life, they are associated with the risk of hypoglycemic episodes and do not prevent the development of debilitating secondary complications. For these reasons, there is increasing demand for new therapies and preventions. One approach is the use of viral or non-viral gene therapy to modify skeletal muscle to produce and secrete insulin into the circulation and/or to increase muscle glucose uptake. Skeletal muscle is a desirable target tissue for the treatment of diabetes not only for its central role in whole body metabolism and glucose homeostasis, but also for its accessibility and amenability to many potential gene therapy technologies. Here, we review the basic metabolic principles of skeletal muscle in the absorptive and post-absorptive states at rest and during exercise and discuss how these processes are affected in type 1 diabetes. Finally, current viral and non-viral strategies for modification of skeletal muscle and their application to the treatment of type 1 diabetes are also presented.

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Cachexia in the non‐obese diabetic mouse is associated with CD4⁺ T‐cell lymphopenia

Cited by 10 publications

References 66 publications

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

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

A Novel Role for CD4+ T Cells in the Control of Cachexia

Skeletal Muscle Metabolism in the Pathology and Treatment of Type 1 Diabetes

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Cachexia in the non‐obese diabetic mouse is associated with CD4+ T‐cell lymphopenia

Cited by 10 publications

References 66 publications

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

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

A Novel Role for CD4+ T Cells in the Control of Cachexia

Skeletal Muscle Metabolism in the Pathology and Treatment of Type 1 Diabetes

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Cachexia in the non‐obese diabetic mouse is associated with CD4⁺ T‐cell lymphopenia