Rapamycin differentially inhibits Th1 and Th2 cell proliferation through mTORC1/S6 kinase pathway

Friday, November 08, 2013 — Poster Session IV
2:00 p.m. – 4:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NIAID	IMMUNO-30

Authors

Y. Yin
C. Prussin

Abstract

Th2 responses are associated with allergies and asthma. Inhibition of mTOR with rapamycin inhibits T cell proliferation and differentiation. In screening for potential anti-Th2 therapeutic targets, we examined rapamycin. Rapamycin inhibition of Th2 proliferation was greater than that for Th1 responses (p< 0.001). Additionally, the inhibition of IL-5+ Th2 proliferation was significantly greater than IL-5- Th2 cells (p = 0.009). At 1 nM rapamycin inhibited IL-5+ Th2, IL-5- Th2, and Th1 responses by 97%, 90%, and 51%, respectively (p = 0.009). Similarly, rapamycin inhibition of anti-CD3-induced proliferation of Th2 cell lines was greater than that of Th1 cell lines (92 vs. 59 %, respectively). Anti-CD3 induction of S6 ribosomal protein (S6rp) phosphorylation was greatest in Th2 cells, relative to either Th1 cells or naïve T cells. Similarly, rapamycin inhibition of S6rp phosphorylation was greatest in Th2 cells, relative to either Th1 cells or naïve T cells.. This preferential inhibition of Th2 proliferation was paralleled by greater inhibition of S6rp phosphorylation, suggesting that rapamycin inhibits Th2 cell proliferation through its inhibition of S6 kinase1. Furthermore, the greater rapamycin sensitivity of IL-5+ Th2 cells suggests that rapamycin and the mTORC1 pathway may be potential therapeutic targets for Th2 driven diseases.