Stem Cell Factor and IL-2 Act Synergistically in Inducing Intraepithelial Lymphocyte Proliferation and Cytokine Production: Upregulation of the IL-2 Receptor γ-Chain and Signaling via JAK-3

Murine intraepithelial lymphocytes (IEL) that express the gamma/delta form of the T cell receptor for antigen (TCRγδ) also express c-kit, the receptor for stem cell factor (SCF). We show here that SCF upregulates the expression of γδ TCR on IEL. More importantly, SCF induces upregulation in the expression of the common γ-chain (γc), which is a shared 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, IFNγ production, non-MHC-restricted cytotoxic activity, and upregulation of the expression of the γc. 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 suggest that SCF may play a more important role in regulating mucosal immune responses than previously appreciated.