Coley, S. M., Ford, M. L., Hanna, S. C., Wagener, M. E., Kirk, A. D. and Larsen, C. P. (2009) IFN- dictates allograft fate via opposing effects on the graft and on recipient CD8 T cell responses. Journal of Immunology, 182(1), pp. 225-233. (doi: 10.4049/jimmunol.182.1.225) (PMID:19109153) (PMCID:PMC2683416)
Full text not currently available from Enlighten.
Abstract
CD8 T cells are necessary for costimulation blockade-resistant rejection. However, the mechanism by which CD8 T cells mediate rejection in the absence of major costimulatory signals is poorly understood. IFN-γ promotes CD8 T cell-mediated immune responses, but IFN-γ-deficient mice show early graft loss despite costimulation blockade. In contrast, we found that IFN-γ receptor knockout mice show dramatically prolonged graft survival under costimulation blockade. To investigate this paradox, we addressed the effects of IFN-γ on T cell alloresponses in vivo independent of the effects of IFN-γ on graft survival. We identified a donor-specific CD8 T cell breakthrough response temporally correlated with costimulation blockade-resistant rejection. Neither IFN-γ receptor knockout recipients nor IFN-γ-deficient recipients showed a CD8 breakthrough response. Graft death on IFN-γ-deficient recipients despite costimulation blockade could be explained by the lack of IFN-γ available to act on the graft. Indeed, the presence of IFN-γ was necessary for graft survival on IFN-γ receptor knockout recipients, as either IFN-γ neutralization or the lack of the IFN-γ receptor on the graft precipitated early graft loss. Thus, IFN-γ is required both for the recipient to mount a donor-specific CD8 T cell response under costimulation blockade as well as for the graft to survive after allotransplantation.
Item Type: | Articles |
---|---|
Additional Information: | This work was supported by National Institutes of Health Grant R37 AI40519-11 (to C.P.L.). |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Coley, Dr Shana |
Authors: | Coley, S. M., Ford, M. L., Hanna, S. C., Wagener, M. E., Kirk, A. D., and Larsen, C. P. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Journal of Immunology |
Publisher: | American Association of Immunologists |
ISSN: | 0022-1767 |
ISSN (Online): | 1550-6606 |
University Staff: Request a correction | Enlighten Editors: Update this record