Table 1.
An overview on included animal studies (n = 24).
| Author and year | Experimental model | Intervention used | Role of T-cells/Findings |
|---|---|---|---|
| Kintscher et al., 2008 [22] | Male C57BL/6 J mice | None | Infiltration of pro-inflammatory T-cells in visceral adipose tissue (AT) preceded that of macrophages. Furthermore, the T-cells were identified in the initiation of AT inflammation and the development of IR. |
| Winer et al., 2009 [12] | RAG-null and diet induced obese (DIO) C57BL/6 J mice | CD4+ T cell transfer | Increased infiltration of pathogenic interferon gamma (IFN-γ) secreting Th1 cells, Th2 and Tregs was identified in an obese state. Moreover, RAG-null mice showed exacerbated obesity and insulin resistance (IR). However, the transfer of CD4+ T-cells into RAG-null DIO mice reversed weight gain and IR. |
| Rocha et al., 2009 [6] | Male DIO C57BL/6 mice | None | Visceral AT of DIO C57BL/6 mice had higher numbers of both CD4+ and CD8+ T-cells than lean controls. In vitro T-cells from obese AT released IFN-γ than in controls |
| Nishimura et al., 2009 [23] | Male DIO C57BL/6 J and CD8null mice | CD8+ T cell transfer | There was increased infiltration of CD8+ T-cells that preceded the accumulation of macrophages in AT of DIO mice. However, genetic depletion of CD8+ T-cells lowered macrophage infiltration and reversed IR. Conversely, the adoptive transfer of CD8+ T-cells to CD8-null mice aggravated AT inflammation |
| Feuerer et al., 2009 [14] Zúñiga et al., 2010 [30] |
DIO C57BL/6 mice Male DIO C57BL/6 J and IL17-null mice |
Anti-IL-2 None |
AT resident Tregs were decreased in obese mice and had no suppressive activity but a normal proliferative response in obesity. Stimulation of Tregs by exogenous anti-interleukin (IL)-2 ameliorated obesity-induced inflammation and IR mediated by increased levels of IL-10 Increased infiltration of IL-17 producing T-cells in obese AT inhibited adipogenesis, moderated infiltration of immune cells in AT and regulated glucose metabolism. Moreover, IL-17 deficient mice developed severe obesity and display altered glucose metabolism compared to the wild type. |
| Yang et al., 2010 [7] | Male DIO C57BL/6 mice were | None | AT T-cells from DIO mice released increased levels of pro-inflammatory cytokines such as IFN-γ upon T-cell receptor (TCR) ligation. Moreover, compared to splenic T-cells, AT T-cells exhibited markedly restricted TCR diversity. Interestingly, removal of T-cells in epidydimal fat enhanced insulin sensitivity in early stage of obesity |
| Strissel et al., 2010 [24] | Male DIO C57BL/6 mice | None | Enhanced priming for IFN-γ production suggested the contribution of CD4+ and/or CD8+ T-cells to cell-mediated immune responses promoting AT inflammation and IR in obesity. T-cell enrichment and IFN-γ gene induction occurred subsequent to AT macrophage recruitment and the development of IR |
| Miller et al., 2010 [33] | Genetically obese diabetic (ob/ob) and ST2-null mice | Recombinant IL-33 | Treatment of AT cultures in vitro with IL-33 induced production of Th2 cytokines, and reduced expression of adipogenic and metabolic genes. Moreover, administration of recombinant IL-33 to ob/ob mice led to reduced adiposity and fasting glucose as well as improved glucose and insulin tolerance. HFD fed mice lacking endogenous ST2 (a receptor for IL-33) had increased body weight, impaired insulin secretion and glucose regulation compared to WT controls on HFD |
| Deiuliis et al., 2011 [3] | Male Foxp3-GFP ‘‘knockin’’ mice | None | DIO resulted in increased CD4+and CD8+ T-cells, with a significantly decreased Treg in visceral AT. Moreover, the number of Tregs inversely correlated with macrophages in the AT. |
| Priceman et al., 2013 [26] | DIO Stat3-null C57BL/6 mice | None | Regulation of AT T cell subsets by transcriptional factor, signal transducer and activator of transcription 3 (Stat3) is crucial for DIO and IR. The activity of Stat3 is elevated in both obese visceral AT and its resident T-cells. Stat3 in T-cells of DIO mice promoted the release of IFN-γ and blunts Tregs in visceral AT. Moreover, mice Stat3 null T-cells showed reduced DIO and improved IR and glucose tolerance, and suppressed visceral AT inflammation. |
| Morris et al., 2013 [27] | Male DIO C57BL/6 J mice | None | High fat diet (HFD)-induced obesity promoted conventional CD4+ T-cell proliferation in mice visceral (AT). Dietary obesity was shown to activate the proliferation of IFN-γ producing CD4+ T cells in adipose tissue |
| Montes et al., 2013 [36] | Male DIO C57BL/6 mice | AntiCTLA-4 Ig and AntiCD40L | CD4+, CD8+ and Tregs were increased in AT of DIO compared to lean controls. However, the administration of co-stimulatory inhibitors in DIO mice reduced inflammation but did not improve glucose tolerance |
| Jiang et al., 2013 [28] | Male DIO CD11-null C57BL/6 J mice | None | CD8+ T-cells in AT of obese mice showed activated phenotypes with increased proliferation and IFN-γ expression. CD11a-null DIO mice displayed markedly reduced T-cell accumulation and activation in AT. Furthermore, CD8+ T-cells from wild type mice, but not from CD11adeficient mice, infiltrated into AT of recipient obese wild type mice |
| Deng et al., 2013 [25] | Male DIO Major histocompatibility complex class II (MHC II)-null C57BL/6 mice | None | Expression MHC II in adipocyte was increased in obesity, which was parallel to increased pro-inflammatory and reduced anti-inflammatory AT T-cells. This exacerbated AT macrophage accumulation and M1 polarisation. Alternatively, MHC II-null mice developed less AT inflammation and IR than wild type mice, despite developing similar adiposity. |
| Zhong et al., 2014 [8] | Male B7-null DIO mice C57BL/6 | Adoptive transfer of Tregs | Reduced B7 expressions in obesity directly impaired Treg proliferation and function in obese mice and led to exacerbated AT inflammation and IR. B7-null mice had enhanced AT inflammation and IR in both obese and lean mice. However, adoptive transfer of Tregs reversed IR and AT inflammation in B7 KO mice. |
| Yi et al., 2014 [9] | DIO CD40-null C57BL/6 mice | None | CD40 deficiency mice exhibited exacerbated AT inflammation and IR with CD8+ T-cells being the major contributor. Contrary to its costimulatory effects, CD40 in fact regulated the development of IR DIO mice by ameliorating AT inflammation. |
| Wolf et al., 2014 [37] | Male DIO CD40-null and Rag1-null C57BL/6 mice | Anti-CD40 antibody Adoptive transfer of CD40-null T-cells |
CD40 deficient mice exhibited increased weight gain, accumulation of inflammatory cells, impaired insulin secretion and enhanced pro-inflammatory gene expression in AT. Conversely, therapeutic activation of CD40 signalling blocked further weight gain, lowered glucose levels, improved insulin sensitivity and suppressed AT inflammation. Furthermore, repopulation of Rag1-null mice with CD40-null T-cells provoked AT inflammation and IR. |
| Fabrizi et al., 2014 [31] | IL-21-null DIO C57BL/6 mice | None | IL-21 and IL-21R mRNA expression was upregulated in DIO and wild type mice in parallel to macrophage and inflammatory markers. Furthermore, DIO IL-21-null mice, showed reduced AT inflammation and improved IR due to increased infiltration of Tregs in AT. |
| Chatzigeorgiou et al., 2014 [10] | Male DIO CD40-null C57BL/6 mice | None | DIO CD40-null mice displayed worsened AT inflammation and IR when compared to wild-type mice. The worsened IR was associated with excessive AT inflammation mediated by increased accumulation of CD8+ T-cells and M1 macrophages. However, CD40L mice ameliorated IR and AT inflammation. |
| Poggi et al., 2015 [38] | Male DIO CD28-null C57Bl/6 mice | Anti-CTLA4 | CD28 deficiency decreased pathogenic T-cells and Treg content within AT without changing macrophages number. CTLA4-Ig injections reduced the number T-cells in AT but not inflammatory cytokines levels |
| Han et al., 2015 [32] | DIO C57BL/6 FOXP3 mice | IL-33 injections | DIO mice exhibited reduced AT-resident ST2+ Tregs thereby promoting inflammation and IR. However, this effect was completely reversed by treatment with IL-33. Furthermore, IL-33 administration also increased the proportion of ST2 expressing Tregs in the AT by 3-fold in DIO mice. |
| Liu et al., 2017 [11] | Male DIO C57BL/6, OX40-KO and B6.Rag2/Il2rg double knock mice | None | Increased expression of OX40 (CD134) on CD4+ T cells, infiltration and expression of pro-inflammatory cells and genes respectively, was observed in the AT of DIO mice. Furthermore, DIO OX40-null mice exhibited significantly reduced weight gain and lower fasting glucose levels than the OX40 knocked in mice. |
| Chen et al., 2017 [15] | Male C57BL/6 J | VAT antigens | Oral treatment of visceral AT mixture antigens effectively inhibited weight gain, and improved IR in HFD mice by increasing the numbers of CD4+Foxp3+ Tregs that were depleted in obesity |