In Vitro Effects of Cyclosporine A and Tacrolimus on Regulatory T-Cell Proliferation and Function

Impact of immunosuppressive drugs on the therapeutic efficacy of ex vivo expanded human regulatory T cells

“…MPA has been shown to inhibit inosine 5'-monophosphate dehydrogenase, a rate-limiting enzyme in the de novo synthesis of guanine nucleotides; thereby it affects DNA synthesis and cell replication of conventional T cells, as well as Tregs. 11 Our results confirmed this negative effect on cell replication in vitro and in vivo when administered as IS …”

“…11,12 Conversely, corticosteroids have been reported to increase Treg frequency and FOXP3 expression in patients with autoimmune diseases. 13,14 Finally, renal transplant recipients receiving MMF show significantly higher CD4…”

Immunophenotypic Profile and Increased Risk of Hospital Admission for Infection in Infants Born to Female Kidney Transplant Recipients

“…This reduction may be related to the fact that calcineurin inhibitors induce apoptosis of T cells (29); azathioprine can lead to leukopenia, further contributing to the reduction in those cells. Calcineurin inhibitors can inhibit the proliferation of regulatory T cells and that could explain the observed decrease in the percentage of these cells (30).…”

Calcineurin Inhibitors: 40 Years Later, Can’t Live Without …

“…Although inhibiting calcineurin in T cells was shown to suppress T cell activation, more recent data suggest a negative effect of CNIs on regulatory T cell proliferation and function (14,15). Regulatory T cells have been shown to be essential for immune tolerance induction in transplantation (16).…”

“…All anatomical structures of the kidney may be involved: arterial hyalinosis is frequently irreversible owing to prolonged vasoconstriction or the regulation of NFAT and smooth muscle (14). Tubulointerstitial injuries classically described as stripped fibrosis and tubular atrophy are multifactorial in origin, resulting from an increase in free radicals (15), an upregulation of TGF-b (16) leading to epithelial to mesenchymal transition (52), or an activation of the reninangiotensin-aldosterone system with an increase in aldosterone (53). Other tubular lesions are seen and include isometric tubular vacuolization and inclusion bodies due to an increase in lysozymes and giant mitochondria (54).…”