Gene Therapy for Modulation of T Cell Mediated Immune Response Provoked by Corneal Transplantation

Pastak M, Kleff V, Saban DR, Czugala M, Steuhl KP, Erguen S, Singer BB, Fuchsluger T (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Human Gene Therapy Mary Ann Liebert

DOI: 10.1089/hum.2017.044

Abstract

Corneal transplantation (=keratoplasty) is the most common type of tissue replacement in the world. The increased rate of graft rejection after keratoplasty is a central problem for repeated transplantations and in inflamed host corneas. It has been shown that apoptosis of grafted epithelium has a role in corneal allograft rejection. Our study focused on the T cell response triggered in BALB/c mice after allogeneic corneal transplantation with and without anti-apoptotic p35-transduced epithelium. To restrict p35 expression to the epithelial cells we created modified allogeneic composite grafts. As a result we found that the proportion of alloreactive CD4+ T cells in postoperatively removed cervical lymph nodes was reduced in the p35-transduced group compared to the allogeneic control group. Diminished priming of the CD4+ T cells was supported by significantly decreased proliferation and lower interferon gamma secretion when compared to allogeneic engraftments. The reduced priming of CD4+ lymphocytes is the first confirmation of the functionality of p35 in the epithelium of corneal grafts to alter the development of the recipient's immune response. Thus, modification of allosensibilization seems to be a promising tool for reducing graft-mediated immune response following corneal transplantation.

Authors with CRIS profile

Thomas Fuchsluger Professur für Augenheilkunde (Cornea/vorderer Augenabschnitt)

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Duke University Health System US United States (USA) (US)

How to cite

APA:

Pastak, M., Kleff, V., Saban, D.R., Czugala, M., Steuhl, K.-P., Erguen, S.,... Fuchsluger, T. (2017). Gene Therapy for Modulation of T Cell Mediated Immune Response Provoked by Corneal Transplantation. Human Gene Therapy. https://doi.org/10.1089/hum.2017.044

MLA:

Pastak, Marko, et al. "Gene Therapy for Modulation of T Cell Mediated Immune Response Provoked by Corneal Transplantation." Human Gene Therapy (2017).

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