Event:1203

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Event Title

Suppression of production of cytotoxic T-cells, Suppression

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
The Adverse Outcome Pathway on binding of FK506-binding protein 12 (FKBP12) by calcineurin inhibitors leading to immunosuppression KE Strong

Taxonomic Applicability

Name Scientific Name Evidence Links

Level of Biological Organization

Biological Organization

How this Key Event works

FK506-FKBP complex interferes with NFAT nuclear localization to suppress the production of multiple classes of cytokines in T cells including L-2, which develops cytotoxic T cells as well as other actions. The suppressive effect of FK506 on mouse MLR, which has been thought to be the representative of IL-2 dependent T cell growth (Kino et al. 1987b). Main mode of actions for suppression of MLR with FK506 deems to result from the decreased production of cytokines including IL-2

How it is Measured or Detected

Suppression of cytotoxic T lymphocyte (CTL) activity can be measured by 51Cr release CTL assay. Suppression of MLR is also measurable by Incorporation of radioisotope (3H-thymidine).

Evidence Supporting Taxonomic Applicability

FK-506 suppresses production of IL-2, IL-3, and IFN-γ in mouse MLR (Kino et al. 1987b). It also suppresses production of cytotoxic T lymphocytes (CTL) (Kino et al. 1987a).In human MLR, as well, FK-506 has been reported to suppress IL-2 production and expression of IL-2 receptors (Kino et al. 1987a).

References

[1] Kino, T., Hatanaka, H., Miyata, S., Inamura, N., Nishiyama, M., Yajima, T., Goto, T., Okuhara, M., Kohsaka, M. and Aoki, H. (1987a). FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. Journal of antibiotics. 40(9): 1256-1265.

[2] Kino, T., Hatanaka, H., Hashimoto, M., Nishiyama, M., Goto, T., Okuhara, M., Kohsaka, M., Aoki, H. and Imanaka, H. (1987b). FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. Journal of antibiotics. 40(9): 1249-1255.