Stem cell factor and IL-2 act synergistically in inducing intraepithelial lymphocyte proliferation and cytokine production: Upregulation of the IL-2 receptor gamma-chain and signaling via JAK-3

Murine intraepithelial lymphocytes (IEL) that express the gamma/delta form of the T cell receptor for antigen (TCR gamma delta) also express c-kit, th e receptor for stem cell factor (SCF). We show here that SCF upregulates th e expression of gamma delta TCR on IEL. More importantly, SCF induces upreg ulation in the expression of the common gamma -chain (gammac), which is a s hared subunit of the receptor complexes for IL-2, -4, -7, -9, and -15. SCF was shown to act synergistically with IL-2 in inducing IEL proliferation, I FN gamma production, non-MHC-restricted cytotoxic activity, and upregulatio n of the expression of the gammac. SCF also acted synergistically with IL-7 and IL-15 in inducing IEL proliferation. IEL exposed to SCF were shown to have enhanced phosphorylation of JAK-3, and when SCF was combined with IL-2 , there was an enhancement in the phosphorylation of JAK-3. These results s uggest that SCF may play a more important role in regulating mucosal immune responses than previously appreciated. (C) 2000 Academic Press.