gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

Iris pigment epithelial cells hijack co stimulatory molecules to convert na´ve T-cells into CTLA-4+, B7-expressing CD8+ regulators

Meeting Abstract

  • corresponding author J. Schwartzkopff - Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, USA; Dept. of Ophthalmology, Albert-Ludwigs University, Freiburg
  • S. Sugita - Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, USA
  • J.W. Streilein - Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, USA

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. DŘsseldorf, K÷ln: German Medical Science; 2004. Doc04dogP 218

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dog2004/04dog709.shtml

Published: September 22, 2004

© 2004 Schwartzkopff et al.
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Outline

Text

Objective

T-cells differentiate into regulatory cells if exposed to ocular pigment epithelia (PE), a mechanism that contributes to the immune privilege of the eye. The goal of this study was to determine the role of molecules of the B7 family expressed by PE during this process.

Methods

PE cells and splenic T-cells were derived from C57BL/6 mice and mice deficient in B7.1, B7.2, CTLA-4 and CD28. Na´ve T cells were exposed to cultured PE cells in the presence or absence of stimulating anti-CD3 Abs, isolated and x-irradiated (PE Tregs). Proliferation of thereafter added T-cells (responder T-cells) plus anti-CD3 Abs was measured by [3H]-thymidine incorporation. Anti-B7.1/B7.2 Abs, recombinant CTLA-4 fusion protein, or anti-CTLA-4 Abs were included in the cultures in which na´ve T-cells and iris PE (IPE) cells were present. Expression of B7.1 & B7.2 by IPE Tregs was assayed by RT-PCR.

Results

Na´ve T-cells, with or without Tcr ligation, acquired the capacity to suppress bystander T cell activation when exposed to all types of PE. This effect was cell contact dependent if IPE Tregs were used and proved to be mediated by B7.1 & B7.2 molecules on IPE. Moreover, CTLA-4, as well as B7.1 & B7.2 expression on T cells were required to acquire the regulatory phenotype. IPE Tregs proved to be almost exclusively CD8+ that secreted active TGFβ.

Conclusions

IPE cells hijack immune co stimulatory molecules to inhibit T-cell pathogenesis in the ocular anterior segment by generating TGFβ-producing CD8+ T-cells. The latter contact and suppress bystander T-cells by similar mechanisms and help to control an overwhelming immune response in the eye.