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The effect of mammalian target of rapamycin inhibition on T helper type 17 and regulatory T cell differentiation in vitro and in vivo in kidney transplant recipients
Author(s) -
Kim Kyoung Woon,
Chung Byung Ha,
Kim BoMi,
Cho MiLa,
Yang Chul Woo
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12351
Subject(s) - peripheral blood mononuclear cell , cd8 , calcineurin , in vitro , in vivo , effector , t cell , sirolimus , chemistry , transplantation , biology , pharmacology , immunology , microbiology and biotechnology , immune system , medicine , biochemistry
Summary Sirolimus ( SRL ) is a promising alternative to calcineurin inhibitors, such as tacrolimus ( TAC ), in kidney transplant recipients ( KTR s), but the immunological benefits of conversion from calcineurin inhibitors to SRL are not fully investigated. In the present study, we evaluated the effect of conversion from TAC to SRL on the T helper type 17/regulatory T (Th17/Treg) axis in three separate studies. First, the effect of SRL on the Th17/Treg axis was evaluated in vitro using peripheral blood mononuclear cells ( PBMC s). Second, the effect of conversion from TAC to SRL on the Th17/Treg axis was studied in KTR s. Finally, the effect of SRL on CD 8 + Treg cells was evaluated. In vitro analysis of PBMC s isolated from KTR s showed that SRL suppressed Th17 cell differentiation but TAC did not. Conversion from TAC to SRL markedly decreased the number of effector memory CD 8 + T cells and significantly increased the proportion of CD 4 + and CD 8 + Treg cells compared with TAC in KTR s. SRL treatment induced the CD 8 + Treg cells, and these cells inhibited the proliferation of allogeneic CD 4 + T cells and Th17 cells. In conclusion, conversion from TAC to SRL favourably regulates Th17 and Treg cell differentiation in KTR s. These findings provide a rationale for conversion from TAC to SRL in KTR s.