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Alveolar Epithelial Type II Cells Induce T Cell Tolerance to Specific Antigen¹

Bernice Lo^*, Soren Hansen, Kathy Evans^*, John K. Heath and Jo Rae Wright^2,*

^* Department of Cell Biology, Duke University Medical Center, Durham, NC 27710; Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark; and School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom

The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type II cells (Type II) constitutively express the class II MHC led us to hypothesize that Type II cells play a role in the adaptive immune response. Because Type II cells do not express detectable levels of the costimulatory molecules CD80 and CD86, we propose that Type II cells suppress activation of naive T cells. Purified murine Type II cells were unable to activate T cells to specific Ag or in an alloreactive assay. Although IFN- treatment up-regulated class II MHC expression, it did not alter the ability of the Type II cells to activate T cells. Rather, the Type II cells were able to suppress T cells from subsequent activation to specific Ag in an Ag-dependent manner. Priming T cells with Type II cells and Ag resulted in T cells that were suppressed to further activation, even after removal from the Type II cells. Thus, Type II cells of the lung help tolerize T cells to nonpathogenic environmental Ags.

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 HL68072 and the Danish Medical Research Council.

² Address correspondence and reprint requests to Dr. Jo Rae Wright, Department of Cell Biology, Box 3709, Duke University Medical Center, Durham, NC 27710. E-mail address: j.wright{at}cellbio.duke.edu

³ Abbreviations used in this paper: Type II, alveolar epithelial type II cell; MHC II, class II MHC; BMDC, bone marrow-derived dendritic cell; ICOSL, inducible T cell costimulator ligand; PD-L1, programmed death-1 ligand 1; PD-L2, programmed death-1 ligand 2; SP-C, surfactant protein C.

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