Wild-type but not interferon-gamma-deficient T cells induce graft arterial disease in the absence of B cells

Cardiovascular Research
Y FurukawaRichard N Mitchell

Abstract

Interferon-gamma (IFN-gamma), a cytokine produced primarily by T cells and by activated macrophages, plays a central role in the pathogenesis of graft arterial disease (GAD). This study investigated whether T cells can induce GAD in the absence of humoral alloresponses and whether activated macrophages or other host cell types can substitute as sources of IFN-gamma in GAD. Wild-type (WT), IFN-gamma-/-, or recombination-activating-gene-1-/- (RAG-1-/-; lacking mature T and B cells) mice received MHC II-disparate hearts. The grafts were harvested 8 weeks post-transplant and histological and immunohistochemical analyses, RNase protection assay (RPA), and flow cytometry were used to evaluate GAD lesions, infiltrating cell populations, and IFN-gamma expression by infiltrating cells. Moderate-to-severe GAD developed in WT recipient allografts, associated with abundant IFN-gamma expression by both infiltrating T cells and macrophages. No GAD developed in IFN-gamma-/- or in RAG-1-/- hosts, nor was any IFN-gamma expression evident. RAG-1-/- hosts receiving naïve WT or IFN-gamma-/- T cells (10(7)) after heart transplantation demonstrated no mature B cells but showed persistence of transferred T cells up to 8 weeks post-transplant. In the ...Continue Reading

Citations

Nov 28, 2007·Annual Review of Pathology·Lynn D CornellRobert B Colvin
Aug 23, 2008·Annual Review of Pathology·Richard N Mitchell
Aug 17, 2004·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·E BinelloO K Harling

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Related Papers

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Howard Eisen, Heather Ross
© 2022 Meta ULC. All rights reserved