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Cutting Edge: Intraepithelial Lymphocytes of the Small Intestine Are Not Biased toward Thymic Antigens¹

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305

T cells, together with β T cells, are abundantly present in the epithelial layer of the small intestine (IEL) and are essential for the host’s first line of defense. Whether or not IELs, like β IELs, are derived from thymocytes that encounter self-Ags in the thymus is unclear. In this study, we report that a natural population of T cells that are specific for the nonclassical MHC class I molecules T10 and T22 are present in the IEL compartment of mice that do not express T10/T22. Furthermore, the small intestinal homing receptor CCR9 is preferentially expressed on thymocytes that have yet to encounter a ligand, and thymocytes with high affinity for self-ligand are CCR9^low. These observations suggest that the Ag-specific repertoire of IELs is not biased toward thymic Ags. Instead, IELs appear suited to respond to novel Ags revealed in pathological settings.

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 National Institutes of Health Grants AI33431 and AI062794 (to Y.-h.C.). K.J. was supported by a Stanford Graduate Fellowship and a Cell and Molecular Biology Training Grant from the National Institutes of Health and S.S. was supported by a National Science Foundation Predoctoral Fellowship.

² K.D.C.J. and S.S. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Yueh-hsiu Chien, 255 Beckman, 279 Campus Drive, Stanford School of Medicine, Stanford, CA 94305. E-mail address: chien{at}stanford.edu

⁴ Abbreviations used in this paper: IEL, intestine intraepithelial lymphocyte; B₂m^–/–, β₂-microglobulin deficient; PI, propidium iodide.