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A more recent version of this article appeared on July 1, 2009
(Investigative Ophthalmology and Visual Science. )
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2982

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Article

Protective Role of {gamma}{delta} T cells in Spontaneous Ocular Inflammation

Rebecca L. O'Brien 1*, Molly A. Taylor 2, Jacqueline Hartley 3, Tanja Nuhsbaum 4, Steve Dugan 5, Kevin Lahmers 6, M. Kemal Aydintug 3, JM Wands 3, Christina L. Roark 3, and Willi K. Born 3

1 Immunology, National Jewish Health, 1400 Jackson St., Denver, Colorado, 80206, United States
2 Univ. of Colorado Denver, Denver, Colorado, United States
3 Immunology, National Jewish Health, Denver, Colorado, United States
4 Ophthalmology, Veterinary Referral Center of Col., Englewood, Colorado, United States
5 Eye Specialists for Animals, Denver, Colorado, United States
6 Veterinary Microbiology, Washington State University, Pullman, Washington, United States

* To whom correspondence should be addressed. E-mail: obrienr{at}njc.org.


   Abstract

Purpose. A role for {gamma}{delta} T cells in immunoregulation has been shown in a number of studies, but in the absence of infection or induced disease, mice lacking {gamma}{delta} T cells generally appear to be healthy. However, we report here that certain mice lacking {gamma}{delta} T cells often spontaneously develop keratitis, characterized by a progressive and destructive inflammation of the cornea. Methods. The keratitis developing in these mice was characterized in terms of prevalence in males vs. females, age of onset, and histological features. Attempts were made to understand the underlying causes of the disease by removing {alpha}{beta} T cells, altering sex hormones, and reconstituting {gamma}{delta} T cells. Results. The development of keratitis in these mice depends upon the C57BL/10 genetic background, and is much more common among females than males. The incidence of the disease increases with age, exceeding 80% in females greater than 18 weeks old. We present evidence that the keratitis in these mice is at least partly autoimmune in nature, and that despite its prevalence in females, male hormones do not protect against the disease. Conclusions. These findings indicate an important role for {gamma}{delta} T cells in maintaining immune balance in the eye. The mice described in this study represent a potential new small animal model of keratitis.

Key Words: ACAID, keratitis, autoimmune response/disease, immune privilege, gamma/delta T cells







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