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T lymphocyte mediated lysis of mitomycin C treated Tenon’s capsule fibroblasts
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  1. J G Crowston1,2,3,
  2. L H Chang1,2,3,
  3. J T Daniels1,
  4. P T Khaw1,2,
  5. A N Akbar3
  1. 1Wound Healing Research Unit, Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK
  2. 2Glaucoma Unit, Moorfields Eye Hospital, City Road, London EC1V 2PD, UK
  3. 3Department of Clinical Immunology, Royal Free Hospital School of Medicine, Pond Street, London NW3, UK
  1. Correspondence to: J G Crowston Hamilton Glaucoma Center, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0946, USA; jcrowstonucsd.edu

Abstract

Aims: To evaluate the effect of T cell co-culture on mitomycin C treated and untreated Tenon’s capsule fibroblasts.

Methods: IL-2 dependent allogeneic T cells were incubated over a monolayer of mitomycin C treated or control fibroblasts. Fibroblast numbers were evaluated by direct counts using phase contrast microscopy. To determine whether T cell mediated lysis was a consequence of MHC mismatch, co-culture experiments were repeated with autologous T cells. The effect of Fas receptor blockade was established by co-incubation with a Fas blocking (M3) antibody.

Results: T cell co-culture resulted in a dramatic reduction in fibroblast survival compared to mitomycin C treatment alone (p = 0.032). T cell killing required fibroblast/lymphocyte cell to cell contact and was observed in both allogeneic and autologous co-culture experiments. Fas blocking antibodies did not significantly inhibit T cell killing (p = 0.39).

Conclusion: T cells augment mitomycin C treated fibroblast death in vitro. Similar mechanisms may contribute to the cytotoxic effect of mitomycin C in vivo and account for the largely hypocellular drainage blebs that are observed clinically.

  • apoptosis
  • glaucoma
  • T cells
  • Tenon’s fibroblasts
  • wound healing
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