T Cells in Adipose Tissue in Aging

Antony, Antu; Lian, Zeqin; Wu, Huaizhu

doi:10.3389/fimmu.2018.02945

Cited by 45 publications

(28 citation statements)

References 117 publications

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“…The increase in effector T cells is mediated by lymphocyte central memory cells. Central memory cells respond to inflammation and obesity-induced metabolic stress by proliferating and attaining an effector memory profile,37 contributing in part to the increase in T cells in adipose tissue during DIO 7 38 39. In our CD4CreCD40L fl/fl mice, we observe a decrease in effector T cells in spleen and lymphoid organs, which is accompanied by a decrease in the expression of the pro-migratory chemokine receptor CXCR3.…”

Section: Discussionmentioning

confidence: 65%

Deficiency of T cell CD40L has minor beneficial effects on obesity-induced metabolic dysfunction

Reiche

Toom

Willemsen

et al. 2019

BMJ Open Diab Res Care

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ObjectiveObesity-associated metabolic dysfunction increases the risk of multiple diseases such as type 2 diabetes and cardiovascular disease. The importance of the co-stimulatory CD40-CD40L dyad in diet-induced obesity (DIO), with opposing phenotypes arising when either the receptor (aggravating) or the ligand (protective) is deleted, has been described previously. The functions of CD40 and CD40L are cell type dependent. As co-stimulation via T cell-mediated CD40L is essential for driving inflammation, we here investigate the role of T cell CD40L in DIO.Research design and methodsCD4CreCD40Lfl/fl mice on a C57BL/6 background were generated and subjected to DIO by administration of 15 weeks of high fat diet (HFD).ResultsHFD-fed CD4CreCD40Lfl/fl mice had similar weight gain, adipocyte sizes, plasma cholesterol and triglyceride levels as their wild-type (WT) counterparts. Insulin and glucose tolerance were comparable, although CD4CreCD40Lfl/fl mice did have a decreased plasma insulin concentration, suggesting a minor improvement of insulin resistance. Furthermore, although the degree of hepatosteatosis was similar in both genotypes, the gene expression of fatty acid synthase 1 and ATP-citrate lyase had decreased, whereas expression of peroxisome proliferator-activated receptor-α had increased in livers of CD4CreCD40Lfl/fl mice, suggesting decreased hepatic lipid uptake in absence of T cell CD40L.Moreover, CD4CreCD40Lfl/fl mice displayed significantly lower numbers of effector memory CD4+ T cells and regulatory T cells in blood and lymphoid organs compared with WT. However, immune cell composition and inflammatory status of the adipose tissue was similar in CD4CreCD40Lfl/fl and WT mice.ConclusionsT cell CD40L deficiency results in a minor improvement of insulin sensitivity and hepatic steatosis in DIO, despite the strong decrease in effector T cells and regulatory T cells in blood and lymphoid organs. Our data indicate that other CD40L-expressing cell types are more relevant in the pathogenesis of obesity-associated metabolic dysfunction.

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Section: Discussionmentioning

confidence: 65%

Deficiency of T cell CD40L has minor beneficial effects on obesity-induced metabolic dysfunction

Reiche

Toom

Willemsen

et al. 2019

BMJ Open Diab Res Care

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“…We speculate that this may be associated with inflammatory CD8 + expansion because recent observations have linked CD8 + T cell and IFN-γ responses with metabolic changes and obesity. 36 Mice administered CD8 + gp350CAR-T cells showed an even higher weight gain (8% at 5 wpi relative to baseline). On the contrary, mice administered CD4 + CD8 + gp350CAR-T cells showed 5% weight loss at 5 wpi (5% at 5 wpi relative to baseline).…”

Section: Resultsmentioning

confidence: 94%

“…To access possible adverse immune-related effects (AIREs) because of CAR-T cell administration in this EBV infection model, we monitored weight, a very important indicator of the health and immunological status of mice and humans. 36 Changes in weight after CAR-T cell administration and EBV infection were plotted relatively to the baseline, the actual day of infection ( Figure 3 E). Interestingly, control mice infected with EBV showed a temporary weight increase along EBV progression.…”

Section: Resultsmentioning

confidence: 99%

CAR-T Cells Targeting Epstein-Barr Virus gp350 Validated in a Humanized Mouse Model of EBV Infection and Lymphoproliferative Disease

Slabik

Kalbarczyk

Danisch

et al. 2020

Molecular Therapy - Oncolytics

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Epstein-Barr virus (EBV) is a latent and oncogenic human herpesvirus. Lytic viral protein expression plays an important role in EBV-associated malignancies. The EBV envelope glycoprotein 350 (gp350) is expressed abundantly during EBV lytic reactivation and sporadically on the surface of latently infected cells. Here we tested T cells expressing gp350-specific chimeric antigen receptors (CARs) containing scFvs derived from two novel gp350-binding, highly neutralizing monoclonal antibodies. The scFvs were fused to CD28/CD3ζ signaling domains in a retroviral vector. The produced gp350CAR-T cells specifically recognized and killed gp350 + 293T cells in vitro . The best-performing 7A1-gp350CAR-T cells were cytotoxic against the EBV + B95-8 cell line, showing selectivity against gp350 + cells. Fully humanized Nod.Rag.Gamma mice transplanted with cord blood CD34 + cells and infected with the EBV/M81/fLuc lytic strain were monitored dynamically for viral spread. Infected mice recapitulated EBV-induced lymphoproliferation, tumor development, and systemic inflammation. We tested adoptive transfer of autologous CD8 + gp350CAR-T cells administered protectively or therapeutically. After gp350CAR-T cell therapy, 75% of mice controlled or reduced EBV spread and showed lower frequencies of EBER + B cell malignant lymphoproliferation, lack of tumor development, and reduced inflammation. In summary, CD8 + gp350CAR-T cells showed proof-of-concept preclinical efficacy against impending EBV + lymphoproliferation and lymphomagenesis.

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“…macrophages and eosinophils in adipose tissue 71 . As samples were randomly recovered from animals slaughtered for human consumption and not for research purposes, no information on the gestational/reproductive status, and lactational stage of the animals could be obtained.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Myeloid Cellular Populations in Mesenteric and Subcutaneous Adipose Tissue of Holstein-Friesian Cows

Oliveira

Pinto

Correia

et al. 2020

Sci Rep

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immune cells resident in adipose tissue have important functions in local and systemic metabolic homeostasis. Nevertheless, these immune cell populations remain poorly characterized in bovines. Recently, we described diverse lymphocyte subpopulations in adipose tissue of Holstein-Friesian cows. Here, we aimed at characterising myeloid cell populations present in bovine adipose tissue using multicolour flow cytometry, cell sorting and histochemistry/immunohistochemistry. Macrophages, CD14 + CD11b + MHc-ii + CD45 + cells, were identified in mesenteric and subcutaneous adipose tissue, though at higher proportions in the latter. Mast cells, identified as SSC-A high CD11b −/+ CD14 − MHcii − CH138A − CD45 + cells, were also observed in adipose tissue and found at higher proportions than macrophages in mesenteric adipose tissue. Neutrophils, presenting a CH138A + CD11b + phenotype, were also detected in mesenteric and subcutaneous adipose tissue, however, at much lower frequencies than in the blood. Our gating strategy allowed identification of eosinophils in blood but not in adipose tissue although being detected by morphological analysis at low frequencies in some animals. A population not expressing CD45 and with the CH138A + CD11b − MHc-ii − phenotype, was found abundant and present at higher proportions in mesenteric than subcutaneous adipose tissue. The work reported here may be useful for further studies addressing the function of the described cells.www.nature.com/scientificreports www.nature.com/scientificreports/ colour-flow cytometry revealed the presence of CD14 + cells, CD172a + cells, CD11c + cells and CD163 + cells in the stromal vascular fraction (SVF) of subcutaneous and omental adipose tissue 23,24 . Recently, Aylward et al. 25 reported the presence of CD172a + CD11b + cells, CD11c + MHC-II + cells, and CD11b + CD11c + cells in mesenteric adipose tissue. However, these markers are not exclusive to macrophages but common to other myeloid cell populations or can be even expressed in non-hematopoietic cells. As an example, studies in humans and mice have shown that CD14 can be expressed in non-myeloid cells 26 such as preadipocytes 27 and epithelial cells 28 . Also, CD172a is expressed by granulocytes such as eosinophils 29 and mast cells 30 beside its expression in monocytes/ macrophages. Since mast cells 31,32 and eosinophils 3,33 have already been described in adipose tissue, single markers analysis limits the interpretation of the data. Therefore, to characterize the different myeloid cell populations in bovine adipose tissue we used a multicolour flow cytometry panel associated with cell sorting and histochemistry/immunohistochemistry analysis. Our strategy allowed identification and isolation of macrophages, mast cells and neutrophils with macrophages being observed at different proportions in mesenteric adipose tissue (MAT) and subcutaneous adipose tissue (SAT). We also showed that CD45 negative cells represent more than 40% of all the cells in the adipose tissue SVF of MAT. A non-leukocyte populat...

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T Cells in Adipose Tissue in Aging

Cited by 45 publications

References 117 publications

Deficiency of T cell CD40L has minor beneficial effects on obesity-induced metabolic dysfunction

Deficiency of T cell CD40L has minor beneficial effects on obesity-induced metabolic dysfunction

CAR-T Cells Targeting Epstein-Barr Virus gp350 Validated in a Humanized Mouse Model of EBV Infection and Lymphoproliferative Disease

Characterization of Myeloid Cellular Populations in Mesenteric and Subcutaneous Adipose Tissue of Holstein-Friesian Cows

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