Journal article
Urinary bladder epithelium antigen induces CD8+ T cell tolerance, activation, and autoimmune response
The Journal of immunology (1950), Vol.178(1), pp.539-546
01/01/2007
DOI: 10.4049/jimmunol.178.1.539
PMCID: PMC4596412
PMID: 17182594
Abstract
The effort to explore the specific autoimmune mechanisms of urinary bladder has long been hindered due to a lack of proper animal models. To better elucidate this issue, we developed a novel line of transgenic (Tg) mice, designated as URO-OVA mice, that express the model Ag OVA as a "self"-Ag on the bladder epithelium. URO-OVA mice are naturally tolerant to OVA and show no response to OVA stimulation. Adoptive transfer of naive OVA-specific T cells showed cell proliferation, activation, and infiltration but no bladder histopathology. In contrast, adoptive transfer of activated OVA-specific T cells induced OVA-mediated histological bladder inflammation. Increased mast cells and up-regulated mRNA expressions of TNF-alpha, nerve growth factor, and substance P precursor were also observed in the inflamed bladder. To further facilitate bladder autoimmunity study, we crossbred URO-OVA mice with OVA-specific CD8(+) TCR Tg mice (OT-I mice) to generate a dual Tg line URO-OVA/OT-I mice. The latter mice naturally acquire clonal deletion for autoreactive OT-I CD8(+) T cells (partial deletion in the thymus and severe deletion in the periphery). Despite this clonal deletion, URO-OVA/OT-I mice spontaneously develop autoimmune cystitis at 10 wk of age. Further studies demonstrated that the inflamed bladder contained infiltrating OT-I CD8(+) T cells that had escaped clonal deletion and gained effector functions before developing histological bladder inflammation. Taken together, we demonstrate for the first time that the bladder epithelium actively presents self-Ag to the immune system and induces CD8(+) T cell tolerance, activation, and autoimmune response.
Details
- Title: Subtitle
- Urinary bladder epithelium antigen induces CD8+ T cell tolerance, activation, and autoimmune response
- Creators
- Wujiang Liu - Roy J. and Lucille A. Carver College of MedicineDavid P Evanoff - Roy J. and Lucille A. Carver College of MedicineXiaohong Chen - Roy J. and Lucille A. Carver College of MedicineYi Luo - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.178(1), pp.539-546
- DOI
- 10.4049/jimmunol.178.1.539
- PMID
- 17182594
- PMCID
- PMC4596412
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 01/01/2007
- Academic Unit
- Urology
- Record Identifier
- 9984320066702771
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