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


METHODS
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.


RESULTS
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)-gamma mRNA expression compared with non-Tg grafts.


CONCLUSIONS
High level expression of vIL-10 in grafts can exacerbate immunological rejection in an allogenic transplantation model.
Adachi
Osamu
O
Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.
Yamato
Eiji
E
Kawamoto
Shunsuke
S
Yamamoto
Mayu
M
Tahara
Hideaki
H
Tabayashi
Koichi
K
Miyazaki
Jun-Ichi
J
D000818:Animals; D005260:Female; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D016027:Heart Transplantation; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D013997:Time Factors; D014184:Transplantation, Homologous; D017211:Treatment Failure
D016753:Interleukin-10