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10.1111/cei.12669

http://scihub22266oqcxt.onion/10.1111/cei.12669
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C4608513!4608513!26077103
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suck abstract from ncbi


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pmid26077103      Clin+Exp+Immunol 2015 ; 182 (2): 230-40
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  • Oscillatory mTOR inhibition and Treg increase in kidney transplantation #MMPMID26077103
  • Sabbatini M; Ruggiero G; Palatucci AT; Rubino V; Federico S; Giovazzino A; Apicella L; Santopaolo M; Matarese G; Galgani M; Terrazzano G
  • Clin Exp Immunol 2015[Nov]; 182 (2): 230-40 PMID26077103show ga
  • Intracellular metabolic pathways dependent upon the mammalian target of rapamycin (mTOR) play a key role in immune-tolerance control. In this study, we focused on long-term mTOR-dependent immune-modulating effects in kidney transplant recipients undergoing conversion from calcineurin inhibitors (CNI) to mTOR inhibitors (everolimus) in a 1-year follow-up. The conversion to everolimus is associated with a decrease of neutrophils and of CD8+ T cells. In addition, we observed a reduced production of interferon (IFN)-? by CD8+ T cells and of interleukin (IL)-17 by CD4+ T lymphocytes. An increase in CD4+CD25+ forkhead box protein 3 (FoxP3)+ [regulatory T cell [(Treg)] numbers was also seen. Treg increase correlated with a higher proliferation rate of this regulatory subpopulation when compared with the CD4+FoxP3? effector counterpart. Basal phosphorylation level of S6 kinase, a major mTOR-dependent molecular target, was substantially maintained in patients treated with everolimus. Moreover, oscillations in serum concentration of everolimus were associated with changes in basal and activation-dependent S6 kinase phosphorylation of CD4+ and CD8+ T cells. Indeed, T cell receptor (TCR) triggering was observed to induce significantly higher S6 kinase phosphorylation in the presence of lower everolimus serum concentrations. These results unveil the complex mTOR-dependent immune-metabolic network leading to long-term immune-modulation and might have relevance for novel therapeutic settings in kidney transplants.
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