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-Producing Dendritic Cells Are Important for Priming of Gut Intraepithelial Lymphocyte Response Against Intracellular Parasitic Infection1
,
* Department of Microbiology, Parasitology and Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112;
Department of Microbiology, Tropical Medicine and Immunology, George Washington University, Washington, DC 20037; and
Department of Medicine and Pathology, Albert Einstein College of Medicine, Bronx, NY 10461
The importance of intraepithelial lymphocytes (IEL) in immunoprotection against orally acquired pathogens is being increasingly recognized. Recent studies have demonstrated that Ag-specific IEL can be generated and can provide an important first line of defense against pathogens acquired via oral route. However, the mechanism involved in priming of IEL remains elusive. Our current study, using a microsporidial model of infection, demonstrates that priming of IEL is dependent on IFN-
-producing dendritic cells (DC) from mucosal sites. DC from mice lacking the IFN- gene are unable to prime IEL, resulting in failure of these cells to proliferate and lyse pathogen-infected targets. Also, treatment of wild-type DC from Peyer’s patches with Ab to IFN- abrogates their ability to prime an IEL response against Encephalitozoon cuniculi in vitro. Moreover, when incubated with activated DC from IFN- knockout mice, splenic CD8+ T cells are not primed efficiently and exhibit reduced ability to home to the gut compartment. These data strongly suggest that IFN--producing DC from mucosal sites play an important role in the generation of an Ag-specific IEL response in the small intestine. To our knowledge, this report is the first demonstrating a role for IFN--producing DC from Peyer’s patches in the development of Ag-specific IEL population and their trafficking to the gut epithelium.
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 A143693 (to I.A.K.) and A131788 (to L.M.W.).
2 Address correspondence and reprint requests to Dr. Imtiaz A. Khan, Department of Microbiology, Tropical Medicine and Immunology, George Washington University, 2300 I Street, Washington, DC 20037. E-mail address: mtmixk{at}gwumc.edu
3 Abbreviations used in this paper: IEL, intraepithelial lymphocyte; DC, dendritic cell; WT, wild type; pf, perforin; PP, Peyer’s patch; CMA, concanamycin A; FasL, Fas ligand; CD95L, CD95 ligand; MLN, mesenteric lymph node.
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  M. M. Moretto, E. M. Lawlor, and I. A. Khan Aging Mice Exhibit a Functional Defect in Mucosal Dendritic Cell Response against an Intracellular Pathogen J. Immunol., December 1, 2008; 181(11): 7977 - 7984. [Abstract] [Full Text] [PDF]
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