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

Wang, Zhuangzhi; Zhao, Chunfang; Moya, Rosa; Davies, Joanna D.

doi:10.4049/jimmunol.181.7.4676

Cited by 36 publications

(35 citation statements)

References 74 publications

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“…Interaction among these factors is not well known. However, a recent report indicates that certain CD4 + T cells might protect against tumor-induced cachexia [40]. We previously found that chronic alcohol consumption in mice bearing subcutaneous B16BL6 melanoma leads to a major loss in body fat which is reflected in a twofold increase in body weight loss at necropsy compared to melanoma-bearing mice drinking water [22].…”

Section: Discussionmentioning

confidence: 99%

Chronic alcohol consumption enhances myeloid-derived suppressor cells in B16BL6 melanoma-bearing mice

Zhang

Meadows

2010

Cancer Immunol Immunother

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We previously found that chronic alcohol consumption decreases the survival of mice bearing subcutaneous B16BL6 melanoma. The underlying mechanism is still not completely understood. Antitumor T cell immune responses are important to inhibiting tumor progression and extending survival. Therefore, we examined the effects of chronic alcohol consumption on the functionality and regulation of these cells in C57BL/6 mice that chronically consumed 20% (w/v) alcohol and subsequently were inoculated subcutaneously with B16BL6 melanoma cells. Chronic alcohol consumption inhibited melanoma-induced memory T cell expansion and accelerated the decay of interferon (IFN)-γ producing T cells in the tumor-bearing mice. Foxp3 + CD4 + CD25 + regulatory T cells were not affected; however, the percentage of myeloid-derived suppressor cells (MDSC) was significantly increased in the peripheral blood and spleen. T cell proliferation as determined by carboxyfluorescein succinimidyl ester labeling experiments in vitro was inhibited by alcohol consumption relative to control water-drinking melanoma-bearing mice. Collectively, these data show that chronic alcohol consumption inhibits proliferation of memory T cells, accelerates the decay of IFN-γ producing CD8 + T cells, and increases MDSC, all of which could be associated with melanoma progression and reduced survival.

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Section: Discussionmentioning

confidence: 99%

Chronic alcohol consumption enhances myeloid-derived suppressor cells in B16BL6 melanoma-bearing mice

Zhang

Meadows

2010

Cancer Immunol Immunother

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“…CD44 int and CD44 v.low cells are equivalent in their ability to generate Th1-type responses. Whether the pro-Th2-type cytokine environment generated by CD44 v.low cells plays a role in their capacity to inhibit cancer cachexia, a syndrome that is strongly associated with inflammation [25] remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, CD44 v.low cells give rise to a large clonally diverse pool with a balanced ratio of naïve and memory cells, and a non-inflammatory cytokine profile. A functional difference between these two cell subsets is further highlighted by the ability of CD44 v.low cells, but not CD44 int cells, to inhibit both diabetes and cancer associated cachexia [25]. …”

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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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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“…CD4 þ T cells that express the lowest density of CD44 (CD4 þ /CD44 very low ) are significantly reduced in cachectic diabetic NOD mice in comparison to noncachectic mice. Wang et al [28] demonstrated that CD4 þ /CD44 very low cells delay the onset of cachexia when infused into recipient mice and, moreover, 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 þ /CD44 very low cells is associated with protection from lymphopenia [28].…”

Section: Cd4 R T Cellsmentioning

confidence: 98%

An update on promising agents for the treatment of cancer cachexia

Madeddu

Mantovani

2009

Current Opinion in Supportive &Amp; Palliative Care

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A number of promising new agents are currently being developed but are not as yet regarded as standard of care. They include: selective COX-2 inhibitors, ghrelin mimetics, oxandrolone, selective androgen receptor modulators (ostarine), olanzapine, anti-IL-6 antibody and an innovative approach of multitargeted combined treatment. The data reported seem to suggest that the most effective treatment for cancer cachexia may be a combination regimen rather than single-agent treatments. This is in keeping with the general consensus that cancer cachexia is a multifactorial process and, hence, a potentially effective approach should be multimodal.

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

Cited by 36 publications

References 74 publications

Chronic alcohol consumption enhances myeloid-derived suppressor cells in B16BL6 melanoma-bearing mice

Chronic alcohol consumption enhances myeloid-derived suppressor cells in B16BL6 melanoma-bearing mice

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

An update on promising agents for the treatment of cancer cachexia

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