Differential Effects of Type I IFNs on the Growth of WC1− CD8+ γδ T Cells and WC1+ CD8− γδ T Cells In Vitro

Abstract

Type I IFNs have a broad array of immunoregulatory functions that include up-regulation of type 1 immune responses through enhancing differentiation and activation of CD8+ T cells and CD4+ Th1 cells. Ovine trophoblast IFN-τ is a recently described type I IFN with the potential for therapeutic use, based on its potent antiviral activity yet low toxicity. Studies were designed to determine the immunoregulatory effects of IFN-τ on Ag-stimulated T cells, and a novel effect of type I IFNs on γδ T cells was observed. In cultures of parasite Ag-stimulated bovine T cells that contained a mixture of αβ and γδ T cells, both IFN-τ and IFN-α suppressed the expansion of WC1+ CD2− CD6− CD8− γδ T cells, yet stimulated the growth of WC1− CD2+ CD6+ CD8+ γδ T cells and CD8+ αβ T cells. The CD8+ γδ T cell subset expressed high levels of the IL-2R α-chain. Furthermore, we showed that type I IFN enhanced IL-2 production by these Ag-stimulated T cell lines. In short term cultures of PBMC, IL-2 stimulated an expansion of WC1− CD6+ CD8+ γδ T cells, which was significantly increased by IFN-τ, even though IFN-τ alone did not support cell survival. These studies demonstrate for the first time that type I IFNs differentially modulate the proliferation of different subsets of γδ T cells, which appears to act in part via IL-2.