CD8+ T cells are involved in early inflammation before macrophages in a rat adipose tissue engineering chamber model

Abstract

Adipose tissues regenerated using tissue engineering chambers (TECs) show the potential for applications in reconstruction of soft tissue defects. Previous studies have shown that early inflammation plays a key role in angiogenesis and adipogenesis required for adipose tissue generation. However, the sequence of events of the early inflammatory cascade is unclear. In this study, we investigated the role of early inflammatory cells in adipose tissue engineering using a rat TEC model. Rats in the TEC model were divided into five groups: the control group, the zymosan A‐treated group, the 5‐AIQ‐treated group, the imatinib‐treated group, and the CD8+ T cell injection group. Fat pad volume, angiogenesis, adipogenesis, inflammatory factor levels, and inflammatory cell infiltration in chambers after implantation were evaluated at different time points. The volume of fat pads of was higher in the zymosan A‐treated and CD8+ T cell injection groups than other groups, and these two groups also showed higher levels of proinflammatory factors, greater numbers of CD31+ cells and perillipin+/Ki67+ cells, and higher macrophage infiltration. The infiltration of CD8+ T cell peaked at 3 days after implantation, which was earlier than that of macrophages. However, inhibition of CD8+ T cells reduced the recruitment of macrophages and lowered inflammation in the TECs. CD8+ T cells played a key role in promoting inflammation at earlier stages than macrophages in adipose TECs. Increased levels of interleukin‐2 secretion by CD8+ T cells resulted in recruitment of more infiltrating macrophages to enhance inflammation, as required for adipose tissue regeneration.

Childhood Adiposity Associated With Expanded Effector Memory CD8+ and Vδ2+Vγ9+ T Cells

“…Previous studies on fat mass and CD8 + T cells showed that mice with obesity had higher CD8 + T cells in adipose tissue (9,37). This increase in CD8 + T cell numbers in adipose tissue and blood has also been observed in adults and adolescents who are overweight or obese (12,15,(37)(38)(39).…”

“…The observed higher number of CD8 + T EM cells in our study and previous studies could be a direct effect of the increased fat mass. A previous study in adipose tissue of adults showed that CD8 + T cell infiltration, and especially the effector memory subset, might be the first immune cell appearance in adiposityinduced inflammation (9,38). The effector CD8 + T cells lack CCR7 expression and are able to directly migrate toward infected or inflamed tissues to execute their effector function (40).…”

“…Adiposity is associated with chronic low-grade inflammation, which predominantly originates in visceral adipose tissue (9)(10)(11)(12). Fat biopsies of adults with overweight or obesity have been shown to be infiltrated with Th1, Th17, and CD8 + T cells, which might be a reflection of this chronic low-grade inflammation (12).…”

“…Adiposity-related inflammation is thought to contribute to the onset of obesity-related morbidity such as insulin resistance (13,16). CD8 + T cells are probably contributors to this adiposity-related inflammation in an early phase by production of pro-inflammatory cytokines, such as interleukin 2 (IL-2), which promote T cell proliferation and adipogenesis (9). In a later phase, the intermediate and nonclassical monocytes are thought to contribute to the adiposity-related inflammation through increased tumor necrosis factor-α (TNF-α) production (13,17,18).…”

Costimulatory Effect of Rough Calcium Phosphate Coating and Blood Mononuclear Cells on Adipose-Derived Mesenchymal Stem Cells In Vitro as a Model of In Vivo Tissue Repair

“…Long-term post-implantation hematoma caused by lateral excursion of the subcutis on the relief CaP surface may play a key role in the vascularization and BMNC invasion required for enhanced tissue regeneration. The infiltration of adipose tissue by T cells peaked earlier than that by macrophages and resulted in the recruitment of additional infiltrating macrophages to enhance inflammation and the reconstruction of soft tissue defects [ 77 ]. Our data emphasize the significance of the T cell status for CaP implantation, which is not always successful at inducing subcutaneous vascularization and bone formation without osteogenic cells or bone growth factors [ 9 , 12 ].…”