Tacrolimus-induced apoptosis and its prevention by interleukins in mitogen-activated human peripheral-blood mononuclear cells

Dendritic cells loaded with FK506 kill T cells in an antigen-specific manner and prevent autoimmunity in vivo

“…Previous work suggests that T cell activation when calcineurin is inhibited leads to antigen specific T cell death (Vanier and Prud'homme, 1992; Migita et al, 1995, 1997; Horigome et al, 1998). To examine the effect of FKDC on T cell survival, CFSE labeled T cells were cultured with allogeneic FKDC or untreated DC and apoptosis was measured by annexin V staining of undivided and postmitotic cells.…”

“…FK506 is a potent inhibitor of calcineurin, a phosphatase stimulated by T cell receptor signaling to regulate the transcription factor nuclear factor of activated T cells (NFAT). Through this mechanism, FK506 inhibits IL2 production (Bierer et al, 1990) and triggers activated T cell death (Horigome et al, 1998; Migita et al, 1999). FK506 also limits the capacity of dendritic cells (DC) to stimulate allogeneic T cell responses in vitro (Woltman et al, 2000; Szabo et al, 2001; Duperrier et al, 2005).…”

Novel apoptosis assay to analyze immunosuppression

“…Nevertheless, the role of immunosuppressive drugs in regulating apoptosis in lymphocytes has not been clearly investigated (1). In fact, earlier studies used purified lymphocytes to determine the effects of immunosuppressive drugs on apoptosis (2–4). However, drug interactions of immunosuppressants can also be determined by analyzing lymphocyte function in whole blood (5).…”

Modulation of Postoperative Scarring with Tacrolimus and Octreotide in Experimental Glaucoma Filtration Surgery

“…21 Previous results were indicated that Tacrolimus efficiently induces apoptosis in mitogen activated human peripheral-blood mononuclear cells. 22 In our study MMC, Tacrolimus and Octreotide One of the most important profibrogenic cytokine is TGF-β which is produced by macrophages, lymphocytes, platelets and fibroblasts, although the main producers of TGF-β are macrophages and fibroblasts. It was reported that TGF-β is potently profibrogenic in conjunctival wound healing.…”