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.
Kathleen B. and Mason Lowance Center for Human Immunology and Rheumatology, Emory University, Atlanta, Georgia 30322, USA. cweyand@emory.edu
Cornelia M
CM
Weyand
Brian R
BR
Younge
Jörg J
JJ
Goronzy
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