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Aging Mice Exhibit a Functional Defect in Mucosal Dendritic Cell Response against an Intracellular Pathogen¹

Department of Microbiology, Immunology and Tropical Medecine, George Washington University, Washington, DC, 20037

Down-regulation of the immune response in aging individuals puts this population at a potential risk against infectious agents. In-depth studies conducted in humans and mouse models have demonstrated that with increasing age, the T cell immune response against pathogens is compromised and response to vaccinations is subdued. In the present study, using a mouse model, we demonstrate that older animals exhibit greater susceptibility to Encephalitozoon cuniculi infection, and their ability to evoke an Ag-specific T cell response at the gut mucosal site is reduced. The dampening of T cell immunity was due to the defective priming by the dendritic cells (DC) isolated from the mucosal tissues of aging animals. When primed with DC from younger mice, T cells from older animals were able to exhibit an optimal Ag-specific response. The functional defect in DC from older mice can be attributed to a large extent to reduced IL-15 message in these cells, which can be reversed by addition of exogenous IL-15 to the cultures. IL-15 treatment led to optimal expression of costimulatory molecules (CD80 and CD86) on the surface of older DC and restored their ability to prime a T cell response against the pathogen. To our knowledge, this is the first report which demonstrates the inability of the DC population from aging animals to prime a robust T cell response against an infectious agent. Moreover, the observation that IL-15 treatment can reverse this defect has far-reaching implications in developing strategies to increase vaccination protocols for aging populations.

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 AI 071778 and AI 043693 awarded to I.A.K.

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: DC, dendritic cell; MLN, mesenteric lymph node; p.i., postinfection.