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Cross Presentation of Antigen on MHC Class II via the Draining Lymph Node after Corneal Transplantation in Mice¹

Lucia Kuffová^*, Magdaléna Netuková^*, Linda Duncan^*, Andrew Porter, Brigitta Stockinger and John V. Forrester^2,*

^* Department of Ophthalmology, Institute of Molecular Sciences and Department of Molecular and Cell Biology, Medical School Foresterhill, University of Aberdeen, Aberdeen, Scotland; and Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom

We investigated Ag trafficking from the cornea and T effector cell activation in secondary lymphoid tissue after corneal transplantation. In preliminary experiments, the central cornea was shown to contain a population of CD45⁺, CD11b⁺, CD11c- cells, with a few MHC class II⁺ cells, and F4/80⁺ cells. However, MHC class II⁺ passenger leukocytes in donor cornea after allografting did not traffic to the draining lymph node. Instead, Ag (plasmid) delivered to the eye via the donor cornea during allograft was detected in host CD11c⁺ and F4/80⁺ APC in the draining lymph nodes and spleen. The earliest detection of APC-associated Ag was at 6 h in the draining lymph node and 24 h in the spleen. After 48 h Ag was not detected in the draining lymph node but was still present in the spleen. Ag applied to the donor corneal epithelium before allografting induced Ag-specific T cell activation and expansion in the draining lymph node with a peak response at 4–6 days, indicating that cross-presentation of Ag had occurred. We conclude therefore, that Ag is transported from the donor cornea within host APC and that this event occurs within hours after grafting. Ag is cross-presented to host CD4⁺ T cells on MHC class II and leads to the activation of Ag-specific effector T cells and clonal expansion in the draining lymph node.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Development Trust of the University of Aberdeen, Aberdeen, Scotland, U.K.

² Address correspondence and reprint requests to Prof. John V. Forrester, Department of Ophthalmology, Institute of Molecular Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, Scotland, U.K. E-mail address: j.forrester{at}abdn.ac.uk

³ Abbreviations used in this paper: DLN, draining lymph node; eGFP, enhanced GFP; Tg, transgenic.