Rapamycin Augments Pathogen-Specific but Not Graft-Reactive CD8+ T Cell Responses

• Authors: Ivana R. Ferrer, Emory University; Maylene E. Wagener, Emory University; Jennifer M. Robertson, Emory University; Alexa P. Turner, Emory University; Koichi Araki, Emory University; Rafi Ahmed, Emory University; Allan D Kirk, Emory University; Christian P Larsen, Emory University; Mandy L Ford, Emory University
• Journal Title: Journal of Immunology
• Volume: Volume 185, Number 4
• Publisher: American Association of Immunologists | 2010-08-15, Pages 2004-2008
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.4049/jimmunol.1001176
• Subjects: Health Sciences, Medicine and Surgery; Biology, Microbiology; Health Sciences, Immunology
• Keywords: CD8+ T cell; immunotherapy; transplantation; heterologous immunity

Abstract

Recent evidence demonstrating that exposure to rapamycin during viral infection increased the quantity and quality of antigen-specific T cells poses an intriguing paradox, since rapamycin is used in transplantation to dampen, rather than enhance, donor-reactive T cell responses. In this report, we compared the effects of rapamycin on the antigen-specific T cell response to a bacterial infection versus a transplant. Using a transgenic system in which the antigen and the responding T cell population were identical in both cases, we observed that treatment with rapamycin augmented the antigen-specific T cell response to a pathogen, while it failed to do so when the antigen was presented in the context of a transplant. These results suggest that the environment in which an antigen is presented alters the influence of rapamycin on antigen-specific T cell expansion, and highlights a fundamental difference between antigen presented by an infectious agent as compared to an allograft.