Spontaneous Corneal Inflammation in gd T cell absence

Summary

Principal Investigator: REBECCA L O'BRIEN
Abstract: The role of gamma-delta T cells in immune responses is still being worked out. Although the cells clearly play an immunoregulatory role, up until now, mice incapable of producing gamma-delta T cells due to genetic inactivation of gamma-delta T cell receptor component (TCR-delta knockout mice) appeared to be largely normal, though defects were apparent when infectious or autoimmune disease was deliberately induced. We recently discovered what we believe to be the first reported spontaneous disease in TCR-delta knockout mice - an inflammation of the cornea that in these mice develops at a high frequency. The keratitis is only apparent when the defective TCR-delta gene is on the C567BL/10 (B10) background. Its incidence increases with age, and it is more common in females than in males. The disease develops slowly, but even in early stages, one can see inflammatory infiltrates in the corneal stroma along with neovascularization. We hypothesize that B10-TCR ( knockout mice develop corneal inflammation because their lack of gamma-delta T cells renders them defective in a mechanism of self-tolerance, which on the B10 background leads to an increased in incidence of spontaneous keratitis. We propose to carry out a pilot/feasibility study to further investigate the origin and features of this disease, and determine whether it is likely to be a useful model for the study of the immunological role of gamma-delta T cells. Our specific aims are: 1. To further define and describe the spontaneous keratitis in B210-TCR delta knockout mice. This will include further recording of the incidence and progression of the disease, as well as an initial investigation into the B 10-derived genes that apparently contribute to the disease. 2. To investigate the mechanisms that lead to the development of spontaneous keratitis in B10-TCR-delta knockout mice. We plan first to examine whether the disease can be improved or prevented by reconstituting affected mice with gamma-delta T cells, or with particular gamma-delta T cell subsets. In addition, we will carryout experiments designed to examine whether the disease is autoimmune, results from bacterial infection, or stems from damage caused by a chemical released from dirty cage litter.
Funding Period: 2004-09-30 - 2007-08-31
more information: NIH RePORT

Top Publications

  1. ncbi The function of gammadelta T cells in innate immunity
    Willi K Born
    Department of Immunology, at National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA
    Curr Opin Immunol 18:31-8. 2006
  2. ncbi Regulatory role of gammadelta T cells in the recruitment of CD4+ and CD8+ T cells to lung and subsequent pulmonary fibrosis
    Philip L Simonian
    Department of Medicine, University of Colorado at Denver and Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
    J Immunol 177:4436-43. 2006
  3. pmc Protective role of gammadelta T cells in spontaneous ocular inflammation
    REBECCA L O'BRIEN
    Integrated Department of Immunology, National Jewish Health, Denver, Colorado 80206, USA
    Invest Ophthalmol Vis Sci 50:3266-74. 2009

Scientific Experts

  • W K Born
  • REBECCA L O'BRIEN
  • Philip L Simonian
  • Brent E Palmer
  • Andrew P Fontenot
  • Ivor S Douglas
  • Christina L Roark
  • Fernando Diaz del Valle
  • Koichi Ikuta

Detail Information

Publications3

  1. ncbi The function of gammadelta T cells in innate immunity
    Willi K Born
    Department of Immunology, at National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA
    Curr Opin Immunol 18:31-8. 2006
    ..Thus, at present, much evidence suggests that gammadelta T cells function in an innate manner, although they are arguably the most complex and advanced cellular representatives of the innate immune system...
  2. ncbi Regulatory role of gammadelta T cells in the recruitment of CD4+ and CD8+ T cells to lung and subsequent pulmonary fibrosis
    Philip L Simonian
    Department of Medicine, University of Colorado at Denver and Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
    J Immunol 177:4436-43. 2006
    ..These findings indicate that chronic inhalation of B. subtilis can result in T cell accumulation in the lung and fibrosis, constituting a new model of immune-mediated pulmonary fibrosis...
  3. pmc Protective role of gammadelta T cells in spontaneous ocular inflammation
    REBECCA L O'BRIEN
    Integrated Department of Immunology, National Jewish Health, Denver, Colorado 80206, USA
    Invest Ophthalmol Vis Sci 50:3266-74. 2009
    ..That certain mice lacking gammadelta T cells often spontaneously develop keratitis, characterized by a progressive and destructive inflammation of the cornea is reported here...