Role of IFNγ in Allograft Tolerance Mediated by CD4+CD25+ Regulatory T Cells by Induction of IDO in Endothelial Cells

Abstract

Regulatory T cells have been described to

The C-Type Lectin-Like Receptor CLEC-1, Expressed by Myeloid Cells and Endothelial Cells, Is Up-Regulated by Immunoregulatory Mediators and Moderates T Cell Activation

“…We previously showed in vitro and in vivo that regulatory CD4 ϩ CD25 ϩ T cells from tolerant recipients were able to stimulate donor-type ECs to express IDO, a molecule required for the establishment of tolerance, demonstrating an interplay between graft ECs and regulatory CD4 ϩ CD25 ϩ T cells for the maintenance of tolerance (10). Here, we also observed that regulatory CD4 ϩ…”

“…We demonstrated that following transfer, regulatory CD4 ϩ CD25 ϩ T cells accumulated in the new graft and induced the expression of IDO in graft ECs (10). Here, we also observed a specific expression of CLEC-1 in ECs in the new allogeneic graft following transfer of regulatory CD4 ϩ CD25 ϩ T cells from tolerant recipients (Fig.…”

“…9). Indeed, we previously demonstrated an accumulation of regulatory Foxp3 ϩ CD4 ϩ CD25 ϩ T cells in tolerated allografts (with up to 15% of CD4 ϩ T cells expressing Foxp3) (10).…”

“…Three days later, cells were pulsed for 8 h with 0.5 Ci/well [methyl-3 H]thymidine (Amersham), and thymidine incorporation was measured using a scintillation counter (TopCount NXT; PerkinElmer). CFSE-labeled cells were stained with anti-TCR, anti-CD4, and intracellularly with anti-Foxp3 Abs as previously described and were analyzed by flow cytometry at day 5 of culture (10). T cells or culture supernatants were harvested at day 3 or 5 of culture for quantitative RT-PCR analysis or cytokine measurement.…”

Infiltrating cellular pattern in kidney graft biopsies translates into forkhead box protein 3 up-regulation and p16INK4α senescence protein down-regulation in patients treated with belatacept compared to cyclosporin A

“…Previous studies demonstrated that concomitant interstitial fibrosis and inflammation in protocol biopsies obtained in the first year correlates with later allograft dysfunction and loss [25]. Finally, belatacept treatment allowed maintaining a stable number of FoxP3 + cells at tissue level which, in turn, could contribute to preserve in-situ tolerance mechanisms [26]. Although the levels of FoxP3 + -expressing cells were not statistically different at 12 months between both group specimens, CsA was associated with a significant decrease of FoxP3 + cell percentages when compared to pre-implantation levels, which is in agreement with a previous study where CsA and rapamycin were compared [27].…”