T cell-mediated inflammation is stereotyped: mouse delayed-type hypersensitivity reaction and mouse T cell-mediated rejection of renal allografts share common molecular mechanismsT cell-mediated inflammation is stereotyped
Date
Author
Institution
Degree Level
Degree
Department
Supervisor / Co-Supervisor and Their Department(s)
Examining Committee Member(s) and Their Department(s)
Citation for Previous Publication
Link to Related Item
Abstract
Genome-wide gene expression analysis of diseases has revealed large-scale changes in the expression of thousands of genes (transcripts) representing biological processes. The processes that occur during T cell-mediated rejection (TCMR) of renal allografts in mice and humans have been previously delineated, and they appear to be independent of cytotoxic mechanisms; thus, TCMR is analogous to delayed-type hypersensitivity (DTH). Since TCMR and DTH involve similar mechanisms, we hypothesized the molecular changes in TCMR are stereotyped; thus, they are qualitatively the same as those in DTH. Using microarrays to compare the transcript expression changes of both diseases in mice, we found they share the same processes: T cell and macrophage infiltration, IFNG-effects, alternative macrophage activation, and a coordinated injury-repair response of the tissue parenchyma. Additional analysis revealed IFNG is vital for stabilizing the injury-repair response in TCMR and DTH. We conclude the molecular changes in TCMR and DTH involve stereotyped, coordinated processes.