Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction

Jae Hyuck Shim, Heung Kyu Lee, Eun Ju Chang, Wook Jin Chae, Jin Hwan Han, Duck Jong Han, Tomohiro Morio, Jung Jin Yang, Alfred Bothwell, Sang Kyou Lee

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47 Citations (Scopus)

Abstract

Tautomycetin (TMC) was identified as an immunosuppressor of activated T cells. Inhibition of T cell proliferation with TMC was observed at concentrations 100-fold lower than those needed to achieve maximal inhibition with cyclosporin A (CsA). TMC specifically blocked tyrosine phosphorylation of intracellular signal mediators downstream of Src tyrosine kinases in a T cell-specific manner, leading to apoptosis due to cleavage of Bcl-2, caspase-9, caspase-3, and poly(ADP-ribose) polymerase, but not caspase-1. In TMC-treated rats that received a heterotopic cardiac allograft, the graft survived more than 160 days, comparable to graft survival in allografted rats treated with CsA. Thus, TMC, whose mechanism of action is different from that of CsA or FK506, can be used as a potent T cell-specific immunosuppressor.

Original languageEnglish
Pages (from-to)10617-10622
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number16
DOIs
Publication statusPublished - 2002 Aug

All Science Journal Classification (ASJC) codes

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