The transplantation of neuronal cells and tissues represents a promising approach for the treatment of incurable neurodegenerative diseases. Indeed, it has been reported recently that retinal transplantation can rescue photoreceptor cells and delay age-related changes in various retinal layers in rodents. However, retinal grafts deteriorate progressively after placement in recipients’ eyes. Here we investigated whether a host’s immune response elicited toward the graft contributes to its deterioration. Using an ELISA spot assay, we measured T cell responses to retinal tissues placed in the vitreous cavity of syngeneic and allogeneic mice. We found that allogeneic retinas induced potent alloimmune responses mediated by T cells secreting type 1 cytokines (IFN-γ and IL-2). No response was found in mice engrafted with syngeneic retinas. In addition, all syngeneic retinal grafts displayed no signs of tissue damage (at 55 days), while the majority of allogeneic retinas deteriorated as early as 12 days after placement. Next, we showed that anti-donor responses occurred within two phenotypically and functionally distinct T cell subsets: CD4+ T cells secreting IL-2 and CD8+ T cells producing IFN-γ. Importantly, CD4+ T cells were necessary and sufficient to cause graft deterioration, while CD8+ T cells did not contribute to this process.
Natalie G. Anosova, Ben Illigens, Florence Boisgérault, Eugenia V. Fedoseyeva, Michael J. Young, Gilles Benichou
Title and authors | Publication | Year |
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Multimodal Delivery of Isogenic Mesenchymal Stem Cells Yields Synergistic Protection from Retinal Degeneration and Vision Loss: Enhanced Vision Rescue via MSC IV Adjuvant Therapy
B Bakondi, S Girman, B Lu, S Wang |
Stem Cells Translational Medicine | 2016 |
A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy
B Lu, Y Lin, Y Tsai, S Girman, G Adamus, MK Jones, B Shelley, CN Svendsen, S Wang |
Translational Vision Science & Technology | 2015 |
Good news-bad news: the Yin and Yang of immune privilege in the eye
JV Forrester, H Xu |
Frontiers in immunology | 2012 |