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CD1-Restricted Recognition of Exogenous and Self-Lipid Antigens by Duodenal ⁺ T Lymphocytes¹

Anna M. Russano^*, Gabrio Bassotti, Elisabetta Agea^*, Onelia Bistoni^*, Alessandro Mazzocchi, Antonio Morelli, Steven A. Porcelli and Fabrizio Spinozzi^2,*

^* Laboratory of Experimental Immunology and Allergy, Section of Internal Medicine and Oncological Sciences, Gastrointestinal and Hepatology Section, Department of Clinical and Experimental Medicine, University of Perugia Medical School, Perugia, Italy; and Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York 10461

T cells are present in the mucosal intestinal epithelia and secrete factors necessary to maintain tissue integrity. Ags recognized by these cells are poorly defined, although in mice non-classical MHC class I molecules have been implicated. Since MHC class I-like CD1 receptors are widely expressed at the surface of epithelial and dendritic intestinal cells and have the capacity to present lipid Ags to T cells, we hypothesized that these molecules might present autologous and/or exogenous phospholipids to intestinal T lymphocytes. Intraepithelial T lymphocytes from normal human duodenal mucosal biopsies were cloned and exposed to natural and synthetic phospholipids using CD1a-, CD1b-, CD1c- or CD1d-transfected C1R lymphoblastoid or HeLa cell lines as APCs. Their cytolytic properties and regulatory cytokine secretion were also examined. Most clones obtained from duodenal mucosa (up to 70%) were TCR⁺, and either CD4⁺ or CD8⁺, whereas 20% were CD4^–CD8^– (6 clones) or TCR⁺ (12 clones). A relevant percentage (up to 66%) of TCR⁺ but few (<5%) TCR⁺ T cell clones responded to synthetic and/or natural phospholipids presented by CD1 molecules, as measured by both [³H]thymidine incorporation and IL-4 release assays. A Th1-like cytolytic and functional activity along with the ability to secrete regulatory cytokines was observed in most phospholipid-specific T cell clones. Thus, a substantial percentage of TCR⁺ but few TCR⁺ from human duodenal mucosa recognize exogenous phospholipids in a CD1-restricted fashion. This adaptive response could contribute to mucosal homeostasis, but could also favor the emergence of inflammatory or allergic intestinal diseases.

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 a grant from the University of Perugia (PROGAT. DELFA99 to F.S.).

² Address correspondence and reprint requests to Prof. Fabrizio Spinozzi, Experimental Immunology and Allergy, Department of Clinical and Experimental Medicine, University of Perugia, Policlinico Monteluce, I-06122 Perugia, Italy. E-mail address: spinozzi{at}unipg.it

³ Abbreviations used in this paper: IEL, intraepithelial lymphocyte; DN, double negative; PC, L--phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PL, phospholipid; iNKT, invariant NKT.