T cells in arteritis and atherosclerosis.
OBJECTIVE
Inflammatory vasculopathies, spanning from atherosclerosis to vasculitides, are driven by innate and adaptive immune responses. Instructed by antigen-presenting cells, T cells have unsurpassed skills to orchestrate protective and pathogenic immunity. Pro-inflammatory and anti-inflammatory T cells regulate master pathogenic pathways, providing a framework for novel immunotherapeutic strategies.


RESULTS
The multilayered wall of macrovessels creates a unique tissue niche; professional antigen-presenting cells, specifically dendritic cells, are superior in triggering and maintaining T-cell responses in this tissue milieu. Plaque-residing dendritic cells sense pathogen-derived motifs and edit inflammatory responses. T cells respond to antigen but antigen-nonspecific factors setting cellular response thresholds may be equally important. Dysregulated signal transduction pathways emerge as highly relevant in biasing T cells toward hyperresponsiveness. In the inflamed atheroma and in arteritic lesions, pathogenic T cells coordinate multiple injury pathways. Besides inducing tissue-damaging macrophage functions, they directly inflict cellular injury within the arterial wall. Distinctively, selected T cells induce smooth muscle cell apoptosis, most prominently by upregulating the death-receptor ligand TRAIL.


CONCLUSIONS
Innate sentinels, specifically dendritic cells, populate normal arteries, intramural vasculitic lesions, and the inflamed atheroma. They sense microbial motifs and instruct T cells toward pro-inflammatory and tissue-destructive effector functions. Microenvironmental factors imposed by the unique structure of the arterial wall appear to be highly conserved across disease entities, modulating inflammation in atherosclerosis and arteritis.
Weyand
Cornelia M
CM
Kathleen B. and Mason Lowance Center for Human Immunology and Rheumatology, Emory University, Atlanta, Georgia 30322, USA. cweyand@emory.edu
Younge
Brian R
BR
Goronzy
Jörg J
JJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001167:Arteritis / Q000276:immunology* / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines