Encapsulated C3HeB/FeJ granulomas show necrotic centers with transcripts associated with immunosuppression (Foxp3, Il10), whereas those in the granuloma rims associate with activated T cells and macrophages.
In a murine glioma model, HGGs induced with FGL2 exhibited a mesenchymal phenotype and increased CD4+ forkhead box P3 (FoxP3)+ Treg cells, implicating immunosuppression as a mechanism for tumor progression.
With the present study, the first evidence is provided that the increase of CD4+CD25 high T cells and FoxP3 transcripts is associated with operational tolerance in liver transplanted patients during IS withdrawal.
The frequency of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly elevated in patients with SSc (3.62±1.14 vs 1.97±0.75, p<0.001) with diminished immunosuppression capacity.
Upon upregulating miR-124 in glioma cancer stem cells (gCSC), the STAT3 pathway was inhibited, and miR-124 reversed gCSC-mediated immunosuppression of T-cell proliferation and induction of forkhead box P3 (Foxp3)(+) regulatory T cells (Treg).
We observed downregulation of unfolded protein response (UPR) and autophagy-related genes (GRP78, IRE1α, ATF4, and Beclin-1) and genes linked to immunosuppression (TGFβ and Foxp3) and upregulation of cytotoxic T-cell marker CD8a in the tumors of the lifetime genistein group, compared with controls, post-diagnosis, and/or adult genistein groups.
Cell culture in vitro demonstrated CD31<sup>+</sup> Tr cells maintaining stable FoxP3 expression after activation and exhibited enhanced proliferation and immunosuppression compared with the CD31<sup>-</sup> subpopulation in T<sub>reg</sub> cells (CD31<sup>-</sup> Tr cells).
Second, regulatory networks, as evidenced by significantly increased expression of Foxp3 (natural regulatory T cell marker) and regulatory effectors such as TGF-beta, CTLA-4, PD-1, ICOS, and indoleamine 2,3-dioxygenase play an important role in immunosuppression.
Immunosuppression led to a significantly altered regulatory marker profile expressed by enhanced TGF-β mRNA production and a reduced frequency of FOXP3+ CD4+ CD3+ cells in solid organ transplanted individuals.
In addition, the expression of forkhead box P3, a characteristic marker of regulatory T cells (Tregs), transforming growth factor‑β1 and interleukin (IL)‑10, inhibitory factors secreted by Tregs and inhibitory costimulatory molecules, cytotoxic T-lymphocyte antigen 4, glucocorticoid-induced TNFR-related protein and programmed cell death protein 1 was observed to be upregulated, indicating that immunosuppression of Tregs was enhanced significantly.
The Treg-ESCs-Mo co-culture treated with E2 (10-8 mol/l) and P (10-8 mol/l) could enhance the immunosuppression of Tregs, as proved by the elevated expression of Foxp3, CTLA-4, CD39 and CD73 on Tregs.
In vitro inhibition of Sirt2 activity enhanced the expression of immunosuppression-associated molecules including forkhead box P3 (Foxp3) in Treg cells.