High-level expression of viral interleukin-10 in cardiac allografts fails to prolong graft survival

Abstract

Viral interleukin (vIL)-10, encoded in the Epstein-Barr virus genome, shares many of the anti-inflammatory properties of cellular IL-10 but is supposed to lack IL-10’s immunostimulatory properties. Thus, vIL-10 is expected to offer superior immunosuppression. We established transgenic mice (vIL-10 Tg) that express vIL-10 systemically and transplanted their hearts as vascularized allografts into unmodified major histocompatibility complex (MHC) full-mismatch or MHC class II-disparate mice. The vIL-10 Tg mice revealed high-level expression of vIL-10 in major organs including the heart. However, the heart grafts from the vIL-10 Tg mice failed to exhibit prolonged survival in combination with either the MHC full-mismatch or the class II-disparate mice. In the MHC class II-disparate mice, the vIL-10 Tg heart grafts showed severe CD8+ T-cell infiltration and increased interferon (IFN)-γ mRNA expression compared with non-Tg grafts. High level expression of vIL-10 in grafts can exacerbate immunological rejection in an allogenic transplantation model.