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Infection and Immunity, June 2007, p. 2708-2716, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01905-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Systemic CD8 T-Cell Memory Response to a Salmonella Pathogenicity Island 2 Effector Is Restricted to Salmonella enterica Encountered in the Gastrointestinal Mucosa{triangledown}

Jessica Jones-Carson,1,2 Bruce D. McCollister,1,2 Eric T. Clambey,3 and Andrés Vázquez-Torres1*

Departments of Microbiology,1 Medicine, University of Colorado Health Sciences Center at Fitzsimons, Aurora, Colorado 80010,2 Integrated Department of Immunology, National Jewish Research and Medical Center, Denver, Colorado 802063

Received 1 December 2006/ Returned for modification 27 February 2007/ Accepted 20 March 2007

To better understand the evolution of a systemic memory response to a mucosal pathogen, we monitored antigen-specific OT1 CD8 T-cell responses to a fusion of the SspH2 protein and the peptide SIINFEKL stably expressed from the chromosome of Salmonella enterica and loaded into the class I pathway of antigen presentation of professional phagocytes through the Salmonella pathogenicity island 2 type III secretion system (TTSS). This strategy has revealed that effector memory CD8 T cells with low levels of CD62L expression (CD62Llow) are maintained in systemic sites months after vaccination in response to low-grade infections with Salmonella. However, the CD8 T-cell pool eventually declines. Low numbers of central memory cells surviving after prolonged resting from an antigen encounter can nevertheless reconstitute the systemic effector memory pool in a route-specific recall response to cognate antigens encountered in the gut. Accordingly, populations of CD62Lhigh interleukin-7 receptor-positive progenitor central memory cells grafted into naïve mice expand in response to orally administered Salmonella expressing the chromosomal translational fusion of sspH2 and the sequence encoding the SIINFEKL peptide but fail to proliferate following systemic stimulation. Moreover, populations of systemic memory CD8 T cells restricted to Salmonella in oral vaccines selectively expand in response to cognate antigens 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.

* Corresponding author. Mailing address: Department of Microbiology, Mail Box 8333, UCHSC School of Medicine at Fitzsimons, P.O. Box 6511, Room P18-9120, Aurora, CO 80010. Phone: (303) 724-4218. Fax: (303) 724-4226. E-mail: andres.vazquez-torres{at}uchsc.edu

{triangledown} Published ahead of print on 2 April 2007.

Editor: A. D. O'Brien

Infection and Immunity, June 2007, p. 2708-2716, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01905-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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