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Infect. Immun. doi:10.1128/IAI.01905-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Systemic CD8 T cell memory to a SPI2 effector is restricted to Salmonella enterica encountered in the gastrointestinal mucosa

Departments of Microbiology and Medicine, University of Colorado Health Sciences Center at Fitzsimons, Aurora, CO 80010; and the Integrated Department of Immunology, National Jewish Research & Medical Center, Denver, CO 80206

^* To whom correspondence should be addressed. Email: andres.vazquez-torres{at}uchsc.edu.

	Abstract

To better understand the evolution of systemic memory to a mucosal pathogen, we monitored antigen-specific OT1 CD8 T cell responses to a stable chromosomal SspH2::SIINFEKL translational fusion loaded into the class I pathway of antigen presentation of professional phagocytes through Salmonella's SPI2 type III secretion system (TTSS). This strategy has revealed that effector CD62L^low memory CD8 T cells are maintained in systemic sites months after vaccination in response to low-grade Salmonella infections. However, the CD8 T cell pool eventually declines. Low numbers of central memory cells surviving after prolonged antigenic resting can nevertheless reconstitute the systemic effector memory pool in a route-specific recall response to cognate antigen encountered in the gut. Accordingly, CD62L^high IL7R⁺ progenitor central memory cells grafted into naïve mice expand in response to SspH2::SIINFEKL⁺ Salmonella administered orally but fail to proliferate following systemic stimulation. Moreover, systemic memory CD8 T cells restricted to Salmonella oral vaccines selectively expand in response to cognate antigen presented by cells isolated from mesenteric lymph nodes (MLN). Together, these findings have revealed the imprinting of systemic CD8 central memory T cell recall responses against enteropathogens by MLN. MLN restriction represents a novel mechanism by which systemic CD8 T cell immunity is confined to periods of high risk for extraintestinal dissemination.