Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 45, Pages 16882-16887Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0607984103
Keywords
autoantibodies; autoimmunity; T lymphocyte
Categories
Funding
- NCI NIH HHS [T32 CA009054, T32 CA 9054] Funding Source: Medline
- NIAID NIH HHS [AI 50831, T32 AI060573, T32 AI 060573, R01 AI050831] Funding Source: Medline
- NIGMS NIH HHS [R37 GM041890, R01 GM041890, GM 41890] Funding Source: Medline
- NINDS NIH HHS [P01 NS018146] Funding Source: Medline
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Sjogren's syndrome (SS) is an autoimmune disease that is characterized by infiltration of exocrine tissues, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Here, we show that mice with T cell-specific loss of class IA phosphoinositide 3-kinase function develop organ-specific autoimmunity that resembles the human disease SS. Most mutant mice aged 3-8 months develop corneal opacity and eye lesions due to irritation and constant scratching. These mice display cardinal signs of primary SS such as marked lymphocytic infiltration of the lacrimal glands, antinuclear antibodies in the serum, and elevated titer of anti-SS-A antibody, in the absence of kidney pathology. Immunofluorescence studies show the presence of numerous CD4(+) T cells with a smaller number of CD8(+) T cells and B cells in the lacrimal glands. CD4(+) T cells from these mice exhibit aberrant differentiation in vitro. These results indicate that aberrant T cells with impaired class IA phosphoinositicle 3-kinase signaling can lead to organ-specific autoimmunity. In addition, the mouse model described here represents a tool to study the pathogenesis and treatment of SS.
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