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In Situ Activation of Antigen-Specific CD8⁺ T Cells in the Presence of Antigen in Organotypic Brain Slices¹

Changying Ling^*, Yakov I. Verbny, Matthew I. Banks, Matyas Sandor^* and Zsuzsanna Fabry^2,*

^* Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School and Department of Anesthesiology, University of Wisconsin, Madison, WI 53706

The activation of Ag-specific T cells locally in the CNS could potentially contribute to the development of immune-mediated brain diseases. We addressed whether Ag-specific T cells could be stimulated in the CNS in the absence of peripheral lymphoid tissues by analyzing Ag-specific T cell responses in organotypic brain slice cultures. Organotypic brain slice cultures were established 1 h after intracerebral OVA Ag microinjection. We showed that when OVA-specific CD8⁺ T cells were added to Ag-containing brain slices, these cells became activated and migrated into the brain to the sites of their specific Ags. This activation of OVA-specific T cells was abrogated by the deletion of CD11c⁺ cells from the brain slices of the donor mice. These data suggest that brain-resident CD11c⁺ cells stimulate Ag-specific naive CD8⁺ T cells locally in the CNS and may contribute to immune responses in the brain.

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 Grant R01-NS 37570-01A2 (to Z.F.).

² Address correspondence and reprint requests to Dr. Zsuzsanna Fabry, Department of Pathology, University of Wisconsin, 1300 University Avenue, 6130 Medical Sciences Center, Madison, WI 53706. E-mail address: zfabry{at}facstaff.wisc.edu

³ Abbreviations used in this paper: MBP, myelin basic protein; ACSF, artificial cerebrospinal fluid; B6, C57BL/6; DC, dendritic cell; DT, diphtheria toxin; DTR, DT receptor; IC, intracerebral; PCC, pigeon cytochrome c; Tg, transgenic.